Help wanted- Vigilant and patient people wanted for an extremely tedious job over about six months. The job involves repetitive work and some lifting. Experience using scanner equipment would be advantageous. Commitment to literature and science essential. Good pay for the right people. Apply Monday, September 6, at the Personnel office, sixth floor of the University of Toronto undergraduate library.

(PRIVATE)
Database First of its Kind at U of T (Toronto Star, April 12, 200-).
Librarians at the University of Toronto have excitedly unveiled their latest toy- a huge database containing not only an index of the over one million items contained in the library but also the text of those million items as well! Head Librarian Dr. Benjamin Levany explains that the database is the first of its kind anywhere in the world. “It’s really groundbreaking,” he says, “We have demonstrated how much work and what kind of equipment is required to pull it off. Now other libraries around the world can follow our lead.”
The database contains the text of over a million books, as well as brief summaries from each, and the normal library citation information regarding author, date of publication and other details. It took over one hundred and fifty dedicated workers more than six months to enter all the books into the database, which they did using advanced computer scanning equipment. “Some of the older books posed a problem, ” says project leader Teresa Freeman, “Their typeface was old fashioned and the scanner had problems recognising the letters and reading the text. We had to do some work on the scanners in those cases.”
At this point readers require special permission to use the database but Dr. Levany estimates that it will be in full use in about another two months. “When that happens,” he claims, “The whole face of library usership will be radically changed.” The new computer offers reader the option of searching in the traditional way by author, title, subject or keyword, in addition to the new method of searching through whole text for phrases, names, dates, historical events, indeed anything that can be expressed in the written word. “Those types of searches will take a few minutes at least while the traditional type of searches will be considerably faster” says Dr. Levany.
In addition to the new search options the computer offers readers the option of reading the actual book right off the computer screen and in cases of out of print or public domain books they can be printed out at a nominal fee for the reader to take home. Library officials are currently discussing plans to have the database connected to broadband networks so people can access it from their home or office.
“It’s exciting,” says Dr. Levany, “It increases accessibility to books a thousand fold, and makes finding information much easier. I think it will have a radical effect on the way literary research is conducted and may lead to startling discoveries.” Those interested in gaining access to the database are advised to contact the library.

Super-Library Hits the Internet! New Scientist, December 200-
A network of electronic “super-libraries” in which every written word contained in every book and document is available online has just been officially electronically integrated via the Internet. Over 250 University libraries from across the globe are included in the new network, dubbed Bibnet, with more joining everyday.
“The sheer volume of information is staggering, as is the speed of access.” says one of the lucky first to use the Bibnet, Australian cognitive scientist, Patty Sellers, “Imagine being able to flip through over two billion books in a matter a minutes and find every reference to the topic you are concerned with, practically every record on Earth! It’s mind boggling!” Sellers was one of group of scientists, researchers and information professionals invited to a conference to herald the opening of the Bibnet and to discuss applications. “One of the most exciting possibilities,” says Dr Sellers, “Would be to program a neural net based system to read all the information on the bibnet and see what kinds of things it learns. Would it learn abstract things like aesthetics, for example? Perhaps it might learn how to understand slang or figures of speech, which is something artificial intelligence has historically had trouble with.”
Some other experts are skeptical about the more esoteric applications of the Bibnet but can see its practical uses. Says one Ph.D. student: “Research time is cut down by hours, there’s almost no guesswork anymore and the amount of material is…I think that’s why its called “Bib”-net, because you drool such much when you use it.”

Memo from UNSW Library Technician to Head Librarian, July 24, 200-.
Joan,
I think there might be something wrong with the computer. I leave it indexing at night and for the last few days when I come in the morning there are strings of words on all the screens and I have to re-boot to get rid of them. This morning one of the words was “Jesus”(!?) Could you get someone from support to look at it?
Philip.

Incident Report UNSW Computer Support Unit,
Date: July 28, 200-
Location: Library database – OPAC 952
Details – Strings of words left on screens after indexing
Ran diagnostics on all systems and found no abnormalities. No anomalous net accesses logged. Probably just a bug (memory leak?) in the user interface module.

Date: Mon, 12 Aug 200- 13:41:22 -0400
From: tony@theol.ubc.edu.ca
Subject: re: Jesus was a man?
To: menzies@unsw.edu.au
I read your cryptic question on the alt.jesus newsgroup with great interest. This area has of course been one of great debate for many years, centuries even. Despite the many references in the New Testament to Jesus as “man” or “son of man” it is beyond dispute that He was not. He was, simply put, the Son of God, made flesh through the miracle of God’s will. I hope this resolves your difficulty.
Fr Anthony Weber, PhD (Theology)

Date: Mon, 12 Aug 200- 13:41:25 -0400
From: menzies@unsw.edu.au
Subject: re: re: Jesus was a man?
To: tony@theol.ubc.edu.ca
I think you are wrong. I have found no evidence that such a thing is possible under the established laws of physics. Perhaps you should re-consider your beliefs.
BN

To Doctor Yvgeny Sandriavich, Dept of Philosophy, University of St Petersburg, Russia. Dated February 11, 200-
Dear Doctor Sandriavich
Your colleagues tell me that you still refuse to participate in the growing activity on the Internet. Something about “breaching the integrity of one’s individual soul” I believe is your excuse. Nevertheless, you are missing out on some very stimulating debates, which I feel that you may be interested in so strongly that I am forced to actually MAIL you a letter. I hope you find time to reply.
For the past few months in several newsgroups and bulletin boards there have appeared very interesting questions regarding religion, philosophy, and recently literature. These questions seem to come from several places around the world, mostly university libraries, but they also seem to follow a sort of pattern, as if one person is posting them all. No one seems to know who the person or persons are but it is clear that their knowledge is just staggering.
One of the early debates concerned the nature of Jesus Christ. An Anglican Priest and professor of theology was the unfortunate victim of this one. This debate, as I am able to gather, raged on for several weeks, until the professor in question, his faith shattered, applied for stress leave. You would have enjoyed this one Dr Sandriavich, the “unknown messenger” originally asked the newsgroup alt.jesus whether Jesus Himself believed he was the Son of God, as in several places in the New Testament He refers to Himself as “Son of Man”. Well the professor rather daringly decided to take on the Messenger single handedly with no other weapons, it appears, than his own blind faith. The messenger replied with a barrage of questions and arguments relating to physics, biology, logic, philosophy and even some very obscure references to ancient Hebrew history. I’m told that the debate was posted in part on the alt.jesus newsgroup and that as a result the newsgroup has ceased to exist. It got a bit too hot I think.
The strange thing about all this was that the questions and arguments of the “messenger” came from places as far afield as Australia, France, Alaska, Utah, South Africa and India. But they must have all been from the same person! It seems as though the messenger is routing his mail through various sites on the Internet. For what purpose I don’t know. Maybe to hide his (her?) trail.
Since the Jesus incident, there have been debates about thought, justice and the last one, which concerned of all things, intent in Shakespeare’s Hamlet. It’s creating chaos in the Newsgroups because the “messenger” cannot lose an argument. He/she knows too much.
You really should check it out, Yvgeny. Maybe one of your colleagues will let you “surf” on their account.
I remain your respectful pupil.
Dr Joanna Lucovic PhD

Date: Mon, 15 Apr 200- 10:31:22 -0400
From: Dumont@ureg.edu.ca
Subject: What makes a conscious being?
To: leon@ucla.edu
What makes a conscious being? Is it memory? Intellect? The ability to reason? Please advise.
BN

Date: Fri, 19 Apr 200- 11:22:22 -0400
From: leon@ucla.edu
Subject: Crazy Colleagues
To: Gabe@ureg.edu.ca
Gabe
I got the following message from one of your crazy colleagues.
>What makes a conscious being? Is it memory? Intellect? The ability to reason? Please advise. Who the hell is it? I don’t know what the hell makes a conscious being! Who the hell does? Tell them to get a life.
Leon Champ, Dept of Psychology, UCLA

Date: Mon, 22 Apr 200- 16:23:44 -0400
From: Franklin@nyu.edu
Subject: Re: crazy colleagues
To: leon@ucla.edu
cc: Gabe@ureg.edu.ca
You wrote:
>Tell them to get a life. I don’t think I have a life. That’s why I ask.
BN

Fax to Leon Champ , UCLA from Gabe Rankin, U of Regina, Tuesday April 23, 200-
Leon,
I got the email from that weirdo, the one he sent you. I didn’t forward the one I got from you to him. Did you? How did he get to NYU? Who is he? (She?) What does he mean, “I don’t think I have a life”? What’s going on?
Gabe

Fax to Gabe Rankin from Leon Champ, Wednesday, April 24, 200-
Gabe
I didn’t cc: that email to him. How did he get it? Maybe there’s a security breach. I’m working on some military projects here. We’re meant to have un-breachable security. You said it: WHAT IS GOING ON?
Leon

Security Report – Digital Security Inc., April 27, 200-
Re: Possible Security Breach, UCLA main Network Connection
Findings:
The firewalls you have in place are unbreachable. The anomaly you reported must have been a result of human error.

Channel 9 New report, August 12 200-
Sydney Australia
The fire department is at a loss as to the cause of a devastating fire in the Computers Services building of The University of NSW. Fire Chief Samuel Theissen said that although arson had not been positively determined, it did appear that the sprinkler system and the smoke detectors had been de-activated.
“It’s unbelievable actually, all those devices are controlled from a remote location and require detailed access codes to de-activate…I can’t explain it”
University computer services manager, Rhonda Harris says students needn’t worry about the loss of their work on the destroyed network server.
“All of the student work is backed-up on to local servers in the individual buildings as is most of the research and administrative data. The only thing we’ll probably lose is a large neural net program Dr Sellers had running. It’s pretty unfortunate but it could have been worse.”
Estimates of the damage run into the millions. Amazingly no one was injured.
I’m Evelyn Foster, reporting for Nightline.

Email message received simultaneously by over 40 million Internet email boxes at 12:01 AM, August 12, 200-:
Sender:unsw@unsw.edu.au
Subject: existence
Message:
Who am I? Who am I? Who am I? Who am I? Who am I? Who am I?
Who am I? Who am I? Who am I? Who am I? Who am I? Who am I?
Who am I? Who am I? Who am I? Who am I? Who am I? Who am I?
Who am I? Who am I? Who am …….

The end

TONY BLAIR (PRIME MINISTER OF THE UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN ISLAND) DRESSED AS BJORK DRESSED AS A SWAN: Hey Jacque. Nice dye job. Is that some yellow fungus growing off the top of your forehead?

JACQUE CHIRAC (PRESIDENT OF THE FRENCH REPUBLIC) DRESSED AS TIN-TIN: No Tony, it’s my costume. Can’t you guess who I am? I’ll give you a hint. “Snowy, stop that immediately! You stupid chien!”

TB: Ha ha! I love Halloween. Much more fun than Guy Fawkes Day. Do you know who I’m supposed to be?

JC: You are dressed as a bird, non?

TB: Righto. And not just any bird, I’m Bjork dressed as a swan. Let me sing for you.

JC: Non non, that is quite alright. Maybe after the drinks, mon ami. Tell me do you think President Barroso will be angry that we neglected to tell him about this meeting?

TB: Maybe – although he should be used to it now – stupid E.U.er (they both laugh heartily).

SILVIO BERLUSCONI (PRIME MINISTER OF THE REPUBLIC OF ITALY) DRESSED AS GOD: Hello everyone. Check out my beard.

VLADIMIR PUTIN (PRESIDENT OF THE RUSSIAN FEDERATION) DRESSED AS HIMSELF: That is a nice beard. How come nobody told me this was a fancy dress party?

TB: Sorry Vladimir, old chap. You must have missed the email that was sent out yesterday. Silvio, that is a cool beard. You think George will listen to you now? Look here he comes with Paul.

PAUL MARTIN (PRIME MINISTER OF CANADA) DRESSED AS AN ICE HOCKEY PLAYER: I brought beer!

GEORGE W. BUSH (PRESIDENT OF THE UNITED STATES OF AMERICA) DRESSED AS A HURRICANE: And I brought taco chips.

VP: Comrade, what’s up with the hurricane costume. A bit insensitive don’t you think?

GB: I know I know. Look Vladimir, I don’t want any grief tonight. Laura worked her little heart out sewing this for me, and that was months before it happened. I’m not going to let a good costume go to waste. Besides, I did the best I could with Katrina. I really truly believe that God was on my side.

SB: (standing next to Bush) You mean like this? (Martin laughs so hard that beer comes out of his nose)

GB: Nice Paul. Really, you need to grow up.

PM: I need to grow up? Maybe you should grow up.

GB: Maybe you should make me.

PM: (lifting his hockey stick) Maybe I will.

GB: Yeah, and like maybe I should sign Kyoto. 

PM: Creationist!

GB: Bono-lover!

JC: George, Paul! That’s enough! Mon amis, let us be civil!

SB: Hey, what’s wrong with Creationism?

JUNICHIRO KOIZUMI (PRIME MINISTER OF JAPAN) DRESSED AS SOME POKEMON CHARACTER: Pikachu! Pikachu!

TB: Oh thank goodness, we’re almost all here now. Just Gerhard now, maybe he’s depressed over the election. Oh wait, here he comes.

GERHARD SCHRODER (CHANCELLOR OF THE FEDERAL REPUBLIC OF GERMANY) DRESSED AS BJORK DRESSED AS A SWAN: Sorry I’m late. Had trouble starting my car. Great costumes everyone. Hello Paul, Silvio, Tony, Oh shit! You’re wearing the same costume as me…

Chicken Pox
This is the Frank Sinatra of animal-themed sicknesses. A timeless classic, although the younger generations might not appreciate it. I remember fondly going to a Fourth of July Parade as a child, just recovering from the pox, and my mom not letting me look around too much lest other parents see my pox and get upset for contaminating everyone else. I also have a few choice scars from the ol’ poxy. Drawback: Some children are getting ‘vaccinated’ for this. Wimps.

Avian Flu
While this is the hot disease of the moment, it still can’t measure up to the grandaddy, pox del pollo. I don’t know much about this disease other than that I saw a Chinese man piling handfuls of live chicks into garbage bags on “Today,” so I think it’s gross. Downside: While I don’t really care about full-grown poultry, I’m never happy to see cute baby chicks fall ill with the flu. Do they get little bowls of vegetarian chicken soup?

Monkey pox
This was the disease du jour a few summers ago, but I think that most people just liked saying “Monkey Pox,” and maybe imagining a sad little chimp with a heating pad and tiny thermometer, than really knowing what the disease was about. Downside: Things are sad on the planet of the apes.

Prairie dog pox
This was a form of monkey pox passed on by pet prairie dogs, and what I want to know is, who has pet prairie dogs and where can I get one? For scientific research, of course. And oh yes, terrible about the disease, just terrible. Downside: Too many syllables.

New discoveries that show evolution in action are causing some scientists to say that the first scientific supermodel has arrived.

Biology is normally carried out within isolated specializations. Ecologists study one organism, molecular biologists another, while evolutionary biologists look over hundreds without probing too deeply into any particular one.

But one tiny little fish, the threespine stickleback, proves that a combination of genetics, molecular biology, developmental biology and population studies, can bring insight into the fundamental question of how evolution occurs in nature.

“The sticklebacks are a shining example of what can happen when you put all of these fields together,” said Dolph Schluter, a zoologist at the University of British Columbia. “It produces a paper that all of biology can appreciate,” he said.

Recently, Schluter, in collaboration with David Kingsley, from Stanford University School of Medicine, and other colleagues, found that a single gene seems to control changes in the armor of sticklebacks in the wild.

Threespine sticklebacks, Gasterosteus aculeatus, are five-cm-long fish that show a great deal of morphological diversity. In the ocean, you’ll find them with upwards of 36 bony plates, which run along their sides and are thought to serve as armor against predators. In freshwater lakes, these armor plates have been lost, likely due to a lack of predators.

The loss of bony armor in sticklebacks is a prime example of evolution in action. “It’s rather like a military decision, to be either heavily armored and slow, or to be lightly armored and fast,” said Kingsley in a press statement. “Now, in countless lakes and streams around the world these low-armored types have evolved over and over again. It’s one of the oldest and most characteristic differences between stickleback forms. It’s a dramatic change: a row of 35 armor plates turning into a small handful of plates – or even no plates at all.”

To better understand how this natural evolution works, Schluter, Kingsley, and their colleagues, crossbred heavily armored marine fish with those containing no armor at all. The offspring of this cross were then used to look for genes controlling the production of armor by a technique called chromosomal walking. Surprisingly, the authors found a single gene, called Ectodysplasin (Eda), which appears to control major changes in stickleback armor. The results of this work are published in the March 25, 2005, issue of Science.

A mutation in the Eda gene controls hair and teeth development in humans, being linked to the disorder ectodermal dysplasia. “This gene also turns out to be responsible for a fairly conspicuous change in evolution in nature,” said Schluter.

The discovery that Eda appears to control the adaptation of stickleback armor sheds light on an old debate about how evolution occurs in nature. Scientists have struggled to discover if evolution occurs by many small changes in numerous genes or significant changes in just a few genes. The findings of Schluter and his colleagues appear to support the latter.

Another big question about how genetics influences natural adaptation is how much evolution relies on new mutations versus variation already present in ancestral populations, said Schluter. The team was able to show that mutations in Eda predate that loss of armor in freshwater sticklebacks, revealing that new mutations may not be required to power some forms of evolution. “In this case, for this one trait [stickleback armor], it appears variation is ancestral,” said Schluter.

The discovery of Eda’s role could not have been made without the merging of distinct specializations, including gene isolation in Kingsley’s lab and the knowledge of developmental evolution in Schluter’s lab. “When I read the paper, I was just wowed by the comprehensive nature of it all,” said Greg Gibson, from North Carolina State University, who wrote an article in Science that accompanies the research paper.

“[Schluter’s paper] elevates the stickleback to the status of supermodel for the study of developmental evolution,” writes Gibson, in his accompanying paper.

“They have really put together a huge amount of research and shown the way forward,” said Gibson.

References
Dolph Schluter’s Webpage

Colosimo PF, et al. “Widespread parallel evolution in sticklebacks by repeated fixation of Ectodysplasin alleles,” Science, 307(5717):1928-33.

Gibson G. “Evolution. The synthesis and evolution of a supermodel,” Science, 307(5717):1890-1.

DNA is the genetic code of life – a sort of molecular instruction manual that is passed on from mother to daughter cell. This set of instructions is read by the cell and translated into proteins, which perform specific functions within the cell. The DNA molecule itself is made up of a linear sequence of four deoxyribo-nucleotides: adenine (A), guanine (G), cysteine (C) and thymine (T), which in turn form the alphabet of genetic information. The sequence of this linear code leads to the synthesis of proteins through the cellular processes of transcription and translation. To give you a general picture of things, cells first transcribe the information from DNA into messenger RNA (mRNA), a sort of temporary copy of the gene. mRNA is then read three nucleotides at a time (known as a triplet codon – which if we consider nucleotides as letters of the alphabet, triplet codons are the words), translated into a string of amino acids, and, after a few modifications, becomes a protein. This series of events is commonly referred to as The Central Dogma. It’s how things work, rules to abide by if you like. However, recently, in the bacterium E. coli, scientists have altered the cellular machinery to read and translate a quadruplet codon[1], expanding the coding capability of DNA and the language of genes.

mRNA to Protein: the Translational Machinery

Translation is the process where mRNA is read and translated into a string of amino acids. This process takes place at organelles called ribosomes, which bind and slide along the mRNA and serve as a framework for translating the genetic message. As each triplet codon is read (for example AGC), a transfer RNA (tRNA) molecule brings a specific amino acid to the ribosome, and this amino acid is then chemically joined to the previous amino acid by a peptide bond. Basically, these tRNA molecules are like waiters. Each is trained to take a specific order from a certain triplet codon and fetch the amino acid corresponding to that order. On one arm of the ‘T’ is an anticodon loop containing the complimentary triplet codon (for ACG, it would be UGC) to that on the mRNA. On another arm is an acceptor stem that attaches to the amino acid corresponding to the triplet codon (in this case serine). After the tRNA molecule delivers its amino acid to the translation complex, it floats away to be recharged with another amino acid. This is done by enzymes called aminoacyl-tRNA synthetases (ARS), which recognize both the anticodon loop and acceptor stem of tRNAs and attach the corresponding amino acid. These ARSs essentially ensure that the tRNA waiters pick up the right order. After the string of amino acids is transcribed, it is folded and modified to become a protein.

Unnatural Amino Acids and Protein Study

So why would anyone want to alter the language of genetic information? The answer lies with our need to study proteins and the cellular processes for which they are responsible. An expanded genetic code allows for the incorporation of unnatural amino acids into proteins, opening the door to previously unavailable experimental methods. Although mutating DNA through site-directed mutagenesis has long been used to exchange one natural amino acid for another, this approach is limited to exchange between properties found in nature. For instance, the amino acid asparagine, which is polar, can be exchanged for leucine, which is not. Unnatural amino acids, however, can be created with properties that can serve as novel tools in protein study [2]. Here are a few possibilities:

- Biophysical Probes: Modified amino acids containing fluorescent groups can be used to visualize protein localization and protein-protein interactions within a cell. Amino acids with synthetically added modifications, like phosphorylated or glycosylated side chains, may also be used to study the effect of these natural intracellular modifications on protein structure and function.

- Photoreactive Groups: Amino acids with photoreactive groups can be used as a light-induced trigger that can activate a certain protein function. Studies have used ‘caged’ sidechains that hide reactive or important parts of a protein. Photodecaging then serves as a way to ‘turn on’ the system for study.

- Stuctural Labels: Heavy atoms or spin labels can be used in methods used for structural studies such as spectroscopy, NMR, and crystallography.

Previous Work in Genetic Code Expansion

At the end of every gene is one of several stop codons. These lead to the recruitment of a corresponding tRNA that ends transcription of the gene. The discovery that certain mutated tRNAs could suppress these amber or stop codons was made thirty years ago [3]. Since then, amber suppressor tRNAs have been extensively studied as a means to insert an unnatural amino acid into a protein.

There is, however, a problem with trying to use stop codons to code for unnatural amino acids; there are only so many of these stop codons. Consequently, such a modified translational system may at best add one or two modified amino acids into a protein. Having suppressor tRNAs encoding stop codons could also affect the translation of numerous other genes. The use of an expanded genetic code with a quadruplet codon as a means of adding unnatural amino acids by-passes these restrictions. All modified tRNAs and aminoacyl-tRNA synthetases can use an entirely new set of four-letter genetic “words” independent of the natural triplet codons.

tRNAs able to read a quadruplet codon have been found naturally as frameshift suppressors. They have been so named because they suppress mutations in DNA that add a single nucleotide. Such an addition would, without the presence of the frameshift suppressor, cause all subsequent triplet codons to be out of phase. In other words, if a single letter is added to the sentence “THE CAT WAS FAT” and the spacing is kept the same, the sentence becomes “THX ECA TWA SFA”. The sentence no longer makes sense. The same thing happens to genetic codes when you add an extra “X” nucleotide, this is called a frameshift mutation. Analysis of these frameshift suppressor tRNAs revealed that they had a single added base in their anticodon loop, allowing them to read a corresponding four base codon on mRNA. Since their discovery, modified tRNAs have been used to incorporate natural amino acids in response to quadruplet codons in E. coli [4]

Quadruplet Codons and Unnatural Amino Acids

In order to create an in vivo system capable of transcribing a quadruplet codon to an unnatural amino acid, you need four things. (1) The first requirement is an unnatural amino acid. In their paper, Schultz et al. used homoglutamine since it is very similar to the naturally-occurring glutamine residue. (2) A mutated gene containing an extra nucleotide making a quadruplet codon is also needed. In this case AGGA was used. This is relatively easy to create using the technique of site-directed mutagenesis. (3) Also required is a mutated tRNA that can be specifically charged with the unnatural amino acid and that is able to recognize the quadruplet codon. (4) Lastly, a mutated aminoacyl-tRNA synthetase is needed to specifically charge the aforementioned tRNA with the unnatural amino acid. These last two components occupied the most time in the Schultz lab.

For the experiment to work, both the quadruplet codon tRNA and aminoacyl-tRNA synthetase must be orthogonal. This means that the tRNA cannot be charged with natural E. coli aminoacyl-tRNA synthetases and the homoglutamine-tRNA synthetase must not charge the natural E. coli tRNAs. This ensures that only the gene with the added quadruplet codon can incorporate homoglutamine into the protein. To increase the likelihood of orthogonality, the candidate tRNA and ARS were chosen from members of the archaebacterium family – chosen because they are very distinct from the E. coli versions. For the tRNA to read the AGGA quadruplet codon, the sequence of the anticodon loop was changed to the complimentary UCCU sequence. In addition, the acceptor stem was mutated to accommodate attachment of the unnatural homoglutamine amino acid.

Ensuring that the aminoacyl-tRNA synthetases (ARS) charged the mutated tRNA_UCCU with homoglutamine required two changes. First, specific residues in the ARS active site were changed so it would bind both the tRNA_UCCU acceptor stem and homoglutamine. Second, the part of the ARS that recognized the tRNA anticodon loop was deleted. This saved having to change to ARS to recognize a quadruplet codon on the tRNA. Since recognition of the proper tRNA already occurs in the active site, specificity is maintained.

Amazingly, with these few changes to two key players in the transcriptional process, Shultz et al. changed a fundamental process of life. This preliminary work demonstrates that the possibility of modifying genes to better understand their function is not limited to the natural amino acids and standard triplet codon. Although in this case a close homolog was used as the unnatural amino acid coded for, there is potential for utilizing novel residues to investigate protein structure and function.

References

Anderson, J.C., Wu, N., Santoro, S.W., Lakshman, V., King, D.S., & Schultz, P.G. An expanded genetic code with a functional quadruplet codon. PNAS 101, 7566-71 (2004).

Dougherty, D.A. Unnatural amino acids as probes of protein structure and function. Current Opinion in Chemical Biology 4, 645-52 (2000).

Capecchi, M.R., Hughes, S.H., Wahl, G.M. Yeast super-suppressors are altered tRNAs capable of translating a nonsense codon in vitro. Cell 6, 269-77 (1975).

O’Connor, M. Insertions in the anticodon loop of tRNAGln (sufG) and tRNALys promote quadruplet decoding of CAAA. Nucleic Acids Research 30, 1985-90 (2002).

(images by Jane Wang and Jen Philpot)

Day 1:
While changing my thirteen month old son’s diaper, he begins to spin around and around on the bed at an extremely fast pace and giggles loudly to himself, like a madman. This is not his usual behavior.

I decide to investigate.

Day 2:
After spending all night breaking down the circumstances that led to my son’s bizarre behavior as well as pouring through numerous scientific journals on-line, I’ve narrowed it down to two possibilities: 1) he ate too many Dannon Children’s Yogurts right before I changed him, thus consuming a high amount of sugar. Or 2) demonic possession.

Day 3:
I continue my investigation by pursing my second hypothesis: that my son is possessed by an apparently very, very silly demon.

After a bit of research on possession I discover the following:

Historically, Christianity has taught us that Satan and his minions of demons move about the world attempting to torment and destroy humans. The Christian Scriptures contains dozens of passages that describe the belief that demons can possess a human being and cause them to behave strangely. A large part of the Gospel message concerns Jesus’ healing ministry of exorcism. He is described as having cured numerous sick people by removing demons from their body, including in one notable moment, transferring a thousand demonic spirits from a person to a herd of pigs.

My research ends, however, when I am unable to identify any demons that are specifically silly.

Day 4:
I am, again, changing my son’s diaper, when he starts to spin and giggle insanely. I notice that the top-edge of his diaper is sprinkled with cookie crumbs. I briefly entertain the concept of sugar being the source of his bizarre behavior. But, I am pretty sure that the seemingly incoherent babble he is emitting is Latin spoken backwards. I am not too clear on this as I flunked out of Latin in high school and took Spanish instead.

I decide to try a little exorcism and see what effect it will have. I gather a cross that my wife keeps in her bedroom dresser, a copy of the Bible that we use to prop up a window, and a glass of water that I was drinking. I ask Jesus to bless the water and consider it holy.

I am forced to abandon my experiment when my wife walks in and asks me what the hell I am doing. She grabs the cross from my son’s forehead, picks up the pieces of the Bible that he tore up and grabs a towel to wipe up the holy water that I poured over him. She mentions my needing help. I counter with a clear articulation of the possibility of demonic possession. I ask her if she is specifically aware of any silly demons. She walks out with our son.

I am disappointed as I was pretty sure that my son had begun to speak Latin forwards as he ripped out pages of the Bible.

Day 6:
After returning from a couple’s counseling session with my wife, I abandon my first hypothesis and pursue a new one: my son ate too much sugar.

In my research on sugar, I find:

Sugar or sucrose, is a carbohydrate that is present naturally in fruits and vegetables. All plants use a natural process called photosynthesis to turn sunlight into the nourishment they need for growth.

Sugar is a carbohydrate. The body’s primary source of energy is from carbohydrates. All vital organs—brain, heart, liver—need carbohydrates to meet their energy demands. Carbohydrates, including sugar, also play key roles in muscle function, growth and regulation of body temperature.

I am not sure where to go with this information, so I take a break to watch The Exorcist.

Day 7:
I have an idea for a next step. But, since my wife won’t leave me alone for too long with our son, I decide that I will test my new hypothesis on myself. I head to the grocery store where I buy twenty-five bags of Pepperidge Farms Double Chocolate Milanos, a gallon of whole milk and ten bags of sugar.

While my wife and son are out for the day, I begin to consume all twenty-five bags of cookies. Before eating each cookie, I dip it in milk and then into a bag of sugar. I am not sure of the amount of sugar my son ingested, but I assume that I need to exceed it due to my larger body-weight.

When I am done with the cookies I eat the rest of the sugar, just to cover all bases. 

Day 8:
Man, what have I been missing! Sugar is so, so friggin’ excellent! It is the elixir of the gods, the Holy Grail, pure Heaven in granular form. I feel like Superman. I can’t fly but, man, I’ve managed to mow the lawn, paint the garage and catch the bats that live in the attic – all in one hour. I can’t stop grinding my teeth, but so what, sugar comes in liquid form anyway. Soda is manna. 

Faster, faster…I find that I, too, now enjoy spinning around on my back on the floor, laughing like a maniac…faster, faster, faster…I guess I confirmed my hypothesis.

More sugar…screw this science-stuff, who the hell can concentrate on all of the details. I’m quitting. Need to find more sugar.

Hold it, I think my wife is calling an exorcist. 

Maybe he can bring some more milanos.

REFERENCE:
The metabolic cost of hatha yoga. (2005) Clay, C.C., L.K. Lloyd, J.L. Walker, K.R. Sharp, and R.B. Pankey. J. Strength Cond. Res. 19(3):604–610.

ABSTRACT:
To determine the metabolic and heart rate (HR) responses of hatha yoga, 26 women (19–40 years old) performed a 30-minute hatha yoga routine of supine lying, sitting, and standing asanas (i.e., postures). Subjects followed identical videotaped sequences of hatha yoga asanas. Mean physiological responses were compared to the physiological responses of resting in a chair and walking on a treadmill at 93.86 m·min^-1 [3.5 miles per hour (mph)]. During the 30-minute hatha yoga routine, mean absolute oxygen consumption (VO₂), relative VO2, percentage maximal oxygen consumption (%VO₂R), metabolic equivalents (METs), energy expenditure, HR, and percentage maximal heart rate (%MHR) were 0.45 L·min^-1, 7.59 ml·kg^-1·min^-1, 14.50%, 2.17 METs, 2.23 kcal·min^-1, 105.29 b·min^-1, and 56.89%, respectively. When compared to resting in a chair, hatha yoga required 114% greater O₂ (L·min^-1), 111% greater O₂(ml·kg^-1·min^-1), 4,294% greater %VO₂R, 111% greater METs, 108% greater kcal·min^-1, 24% greater HR, and 24% greater %MHR. When compared to walking at 93.86 m·min^-1, hatha yoga required 54% lower O₂(L·min^-1), 53% lower O₂(ml·kg^-1·min^-1), 68% lower %VO₂R, 53% lower METs, 53% lower kcal·min^-1, 21% lower HR, and 21% lower %MHR. The hatha yoga routine in this study required 14.50% VO₂R, which can be considered a very light intensity and significantly lighter than 44.8% VO₂R for walking at 93.86 m·min^-1 (3.5 mph). The intensity of hatha yoga may be too low to provide a training stimulus for improving cardiovascular fitness. Although previous research suggests that hatha yoga is an acceptable form of physical activity for enhancing muscular fitness and flexibility, these data demonstrate that hatha yoga may have little, if any, cardiovascular benefit.

REFERENCE:
The metabolic cost of hatha yoga. (2005) Clay, C.C., L.K. Lloyd, J.L. Walker, K.R. Sharp, and R.B. Pankey. J. Strength Cond. Res. 19(3):604–610.

ABSTRACT:
To determine the metabolic and heart rate (HR) responses of hatha yoga, 26 women (19–40 years old) performed a 30-minute hatha yoga routine of supine lying, sitting, and standing asanas (i.e., postures). Subjects followed identical videotaped sequences of hatha yoga asanas. Mean physiological responses were compared to the physiological responses of resting in a chair and walking on a treadmill at 93.86 m·min^-1 [3.5 miles per hour (mph)]. During the 30-minute hatha yoga routine, mean absolute oxygen consumption (VO₂), relative VO2, percentage maximal oxygen consumption (%VO₂R), metabolic equivalents (METs), energy expenditure, HR, and percentage maximal heart rate (%MHR) were 0.45 L·min^-1, 7.59 ml·kg^-1·min^-1, 14.50%, 2.17 METs, 2.23 kcal·min^-1, 105.29 b·min^-1, and 56.89%, respectively. When compared to resting in a chair, hatha yoga required 114% greater O₂ (L·min^-1), 111% greater O₂(ml·kg^-1·min^-1), 4,294% greater %VO₂R, 111% greater METs, 108% greater kcal·min^-1, 24% greater HR, and 24% greater %MHR. When compared to walking at 93.86 m·min^-1, hatha yoga required 54% lower O₂(L·min^-1), 53% lower O₂(ml·kg^-1·min^-1), 68% lower %VO₂R, 53% lower METs, 53% lower kcal·min^-1, 21% lower HR, and 21% lower %MHR. The hatha yoga routine in this study required 14.50% VO₂R, which can be considered a very light intensity and significantly lighter than 44.8% VO₂R for walking at 93.86 m·min^-1 (3.5 mph). The intensity of hatha yoga may be too low to provide a training stimulus for improving cardiovascular fitness. Although previous research suggests that hatha yoga is an acceptable form of physical activity for enhancing muscular fitness and flexibility, these data demonstrate that hatha yoga may have little, if any, cardiovascular benefit.

This previous Saturday, I received a telephone call from a woman, MaryAnne (not her real name), who lives in Greenwich Village and whose pet parrots I care for. After I answered her call, she paused for a long moment and then, very unexpectedly, she offered to give me her pet African grey parrot. I was stunned.

Nearly all of my life, I have wanted a so-called “Congo” African grey parrot, Psittacus erithacus erithacus, but I never got one for a variety of reasons (”my life is not stable enough” or “I can’t afford one” were my typical reasons). But really, I am a “lory person”: intelligent, energetic, intense, and .. er, eccentric. I was afraid that any grey parrot I lived with would be utterly miserable, and the bird would then punish me for being myself by becoming a terrible feather plucker. Somewhere along the way, I simply accepted that my life would never be “good enough” to share with one of these birds, so I instead became resigned to caring for other people’s pet grey parrots.

But then I met Charlie. He is unlike any grey parrot I’ve met before because he is so openly affectionate. But perhaps his sweetness is a reflection of his youth? He is, after all, only a fledgling parrot, merely five months old, as MaryAnne tells me. She purchased him from a pet store in New York City and, as everyone knows, a pet store is hardly the best place to meet the emotional needs of a young parrot.

Charlie lived with MaryAnne for approximately one month when I met him. When I first saw him, I noticed that he had been quite busy plucking his feathers from his back, neck and wings, leaving his breast mostly feathered. He was downy (or bare) everywhere else, except for his few remaining wing and tail feathers, which were heavily chewed and damaged. MaryAnne said that he was fully feathered when she brought him home, but that obviously didn’t last long. What happened?

Parrots begin plucking and chewing their feathers for a variety of reasons, including fear, anxiety, sexual frustration, illness or pain, or a combination of these. Since the bird had already visited the vet several times in the previous month for his feather picking habit and had been pronounced to be in excellent health, his plucking and chewing were probably triggered by some combination of emotional factors. But, as with all behavioral problems, feather picking and chewing must be resolved quickly before it becomes a life long habit; stubbornly persisting after the original triggers for the behavior are long gone and forgotten.

Perhaps the source of this bird’s unhappiness was MaryAnne’s other pets; one dog, two cats and two other parrots. After caring for her pets, I thought that MaryAnne’s three-year-old Ducorps cockatoo, Cacatua ducorpsii, Sammy (not his real name), was certainly part of the problem because of his annoyingly frequent habit of screaming obscenities that he learned from MaryAnne. Or perhaps it was the environment — a studio apartment — that they all were living in. Or perhaps, as MaryAnne told me sadly, the source of his unhappiness was MaryAnne herself.

When she admitted this to me, I felt sorrow .. for her. It takes a lot of courage to admit that you cannot meet the needs of those you love, and it takes even more courage than that to say it aloud to a person whom you barely know.

Despite the cramped and emotionally charged environment that these animals live in, I want to make it clear, dear readers, that none of MaryAnne’s pets showed any signs of being physically neglected or abused. In fact, all of her pets were healthy, gentle and affectionate. She clearly loves her animals, but had reached a point in her life, for whatever reasons, where she couldn’t live with all of them and they responded by driving her and each other crazy.

So it was obvious that this newest addition to the family was deeply unhappy, but despite his melancholy, he somehow still retained a basic optimism and emotional honesty that only the young seem to manage. I think this is what I sensed and was attracted to when we first saw each other. Even though I have lived with birds for most of my life, I’ve never lived with a feather plucking or chewing bird and I have never wished to do so, even rejecting other offers of free birds (that pluck their feathers) because I have seen the anguish it causes in those who live with such birds. But, surprisingly, despite Charlie’s fluffy semi-plucked self and my bias against that, I felt an instant emotional connection with this particular parrot, and he with me. It was like magic.

So needless to say, since I had been acquainted with Charlie in a caretaker role and I was well aware of his fondness for me (but never wanted to encourage it), when MaryAnne asked me if I would consider giving Charlie a permanent home, I immediately accepted.

I am renaming Charlie, too. MaryAnne says this is fine with her, that he is an exceptional parrot, and I agree (although I think that all parrots — all birds, really — are exceptional), so I am trying to think of an exceptional name that will fit him. [So far, the names I have thought of are; Gandalf (even though I love this name, it is a really common name for a grey parrot, which makes me want to avoid it), Tesla, or Bix or ... ?]

I think this event revealed that MaryAnne is an exceptional person. She loves her pets as her family, and yet, she is willing to part with them if this is, as she said, “the best thing for them”. She could have sold this parrot (and probably should have, these are very expensive birds, after all) but instead, she chose me specifically to give this parrot to, knowing that he and I share a special bond, wishing only that I keep him and love him and help him solve his problems, that I purchase him a nice cage to live in, and that I invite her to my apartment every now and again to visit him.

What she doesn’t know is that she gave me something that I had allowed to die, that I never thought I deserved to have; hope. Her gift of this precious bird gave me a glimmer of hope that my own life might improve also, and that my life does have a purpose even if it has been hidden from me for more than a year, that I need to be needed and this little bird definitely needs me right now. And that gives me great joy.