Tuesday, November 14, 2006

A silly hypothetical question is answered

I just found out, via digholes.com, that if I were to dig a hole straight through the center of the earth I would come out almost exactly on a line linking the southernmost points of Africa and Australia, a little under half as far from the former. So, if I could build something that could survive passage through all that molten rock, and still have enough energy to overcome the gravitational pull and get back out, I would have plenty of water on the other side to cool my amazing contraption down again at the other end. Nice to know.

Wednesday, November 01, 2006

The history of drugs in music

I don't think anyone reading this will be surprised that drugs and musicians tend to go together, particularly in the rock and rap scenes. Nevertheless, I thought I'd post this article from music news site Blender.com for whoever needs to be reminded how much of the musical creativity and productivity we admire has been facilitated by psychoactive chemicals in one way or another. Even if you are like me and don't doubt that fact, unless you are an expert in the history of drugs in the music scene, I bet you will learn something from reading this.

Saturday, October 14, 2006

Backwards (pseudo)science

Most people have probably heard claims of hidden messages in popular songs that are revealed when the sound is played in reverse. I suspect also that most see these things as nothing more than amusing coincidences.

Today I came across the website of a man, David John Oates, who has created an entire business around this idea. He claims things as outlandish as that children learn to speak in reverse when babbling before they learn to speak forward, and that the sound of a lie, when played backwards, will reveal the truth. He ties all this to the hypothesis that human speech contains two components, a conscious forward part and a subconscious reverse part. He claims that this supposedly revolutionary idea is useful for lie detection in criminal trials, selection of the best business strategy, and a bunch of other things, and offers to listen to a 5 minute tape backwards for $125 in order to pick out any subliminal messages.

One piece of "evidence" he uses to back up his theory is a study of recordings of subjects made to read identical passages, which were analyzed to determine if the phrases appearing in reverse were the same for all subjects. Also, the number of reversals for people reading an emotional and neutral passage were compared. The data analysis for this experiment is a brilliant example of bad science. In particular, the authors reason that if the reversals were coincidental, they would be the same for all subjects reading the same phrase forward. Any scientist knows this is a ridiculous assertion--coincidental results show MORE variability than ones that are indicative of some underlying phenomenon. In addition, the authors expected to find more hidden messages in the speech of the people reading the emotional passages, while in fact they found the opposite. Most importantly, any use of statistical tests of significance is totally omitted from the analysis. As there were only two subjects reading each passage, using such tests would inevitably reveal the results to be insignificant.

I seriously wonder who would pay $125 or more to have someone listen for these messages in speech, but seeing the non-trivial popularity of psychics maybe one shouldn't be so surprised.

Friday, August 18, 2006

Bacteriophages to be used to prevent food poisoning

The FDA has recently approved the use of a mixture of bacteriophages, or viruses that infect bacteria, for spraying on meat before packaging in order to kill the disease-causing bacterium Listeria. This is likely the first significant practical application of bacteriophages outside of the laboratory. Hopefully, the use of multiple types of virus will prevent the emergence of Listeria strains resistant to destruction.

Saturday, July 29, 2006

Knocking out stimulant reward

The article I'm reporting here is a little over a month old, but now that I'm getting around to updating my blog I thought I'd mention it. For those that don't know, the modified amino acids dopamine, norepinephrine, and serotonin, collectively known as monoamines, are neurotransmitters that are released by specific neurons in the brain and activate receptors on other neurons, sending a message from one cell to another. There are "pumps" in the membranes of the neurons that release these transmitters, which "clean up" the released monoamines so that they don't keep activating receptors for too long. These pumps are blocked by many psychotherapeutic and recreational drugs, producing a change in brain function. While each neurotransmitter has multiple effects in the brain, the transmitter dopamine in particular is believed to participate in the behavior-reinforcing properties of both natural (food, sex, etc.) and pharmacological (drug) stimuli. Among many scientists dopamine is still believed to be a kind of "pleasure chemical" whose concentration determines the degree of poitive subjective sensation produced by the environment, regardless of the specific nature of the stimulus. This idea has been called into question especially lately, though, for a number of reasons, many of which have nothing to do with this article. For instance, the effect of drugs that directly activate dopamine receptors is not euphoric in humans.

The finding that concerns us here is one made by Sora et. al. in 1998. To understand the significance of this study, it is important to know that the stimulant cocaine blocks the transporters ("pumps") for all three monoamines. Given the assumed responsibility of dopamine for reinforcement, it has long been assumed that blocking the dopamine transporter (DAT) produces the euphoric effect of cocaine by allowing dopamine to sit around and activate its receptors longer. To test this, Sora et. al. deleted ("knocked out") the gene encoding DAT from mice, and showed that they still prefer to spend time in a chamber in which they have previously received cocaine. This so-called conditioned place preference suggests that cocaine can act as a reward even when it cannot block DAT (because DAT doesn't exist in these mice). Knocking out the serotonin transporter (SERT) also left cocaine reward intact. A follow-up study showed that knocking out both DAT and SERT makes mice that do not prefer an environment they associate with cocaine. Sora et. al. took this to mean that blocking SERT is rewarding as well, which flies in the face of the fact that blocking SERT with drugs like fluoxetine (Prozac) does not produce signs of euphoria. An obvious caveat here is that the brains of DAT knockout mice are flooded with dopamine and the animals are very hyper even when they aren't on any drugs, so findings may not generalize to normal mice.

The new study by Chen et. al. took a different approach. They found that by mutating part of DAT, they could prevent cocaine from binding to it without breaking the pump. When this mutant DAT was added back into DAT knockout mice, cocaine no longer made the mice hyperactive like it does normal mice (paradoxically, it calmed them) and was not rewarding. This confirms what I--and probably many other researchers--suspected was going on: the mice with DAT knocked out only showed a response to cocaine because it slightly amplified the effect of the high baseline dopamine. Possible explanations are that increased activation of serotonin receptors overcomes some negative feedback mechanism limiting dopamine levels, or that lack of DAT induces a form of plasticity in the reward pathway such that SERT blockade becomes rewarding. This still doesn't explain other results questioning the idea of dopamine as a "pleasure chemical", but at least it shows that cocaine, and probably methylphenidate (Ritalin) and amphetamines, do produce their reinforcing effects through inhibition of dopamine reuptake.

Wednesday, July 26, 2006

What is the soundtrack of our genome?

A few days ago I took a look at Mendel's Garden #3, and among the featured post is a discussion of the work of Japanese biologist Susumu Ohno. He took a part of the gene encoding the large subunit of RNA polymerase II and converted it into music, considering both the base sequence itself and the properties (size and charge) of the encoded amino acids. He thought that this piece sounded like a Chopin nocturne, so he took the nocturne and "reverse translated" it to a DNA sequence. He proceeded to demonstrate that this sequence contains a 160-codon open reading frame (see this site for more), and went on to make lots of philosophical speculations about how DNA sequences and music evolve in the same manner. The probability that any given sequence of 160 base triples would start with a start codon and not contain stop codons is a little less than 1/130,000. However, this could be artificially raised by many orders of magnitude by assigning the start and stop codons to sequences of notes that are very frequent and rare, respectively, in the nocturne, which shouldn't be difficult to find with the right software.

Perhaps most interesting is the musician Colin Angus of the group The Shamen, who teamed up with biologist Ross King to create the piece "S2 Translation" containing the full sequence of a serotonin receptor. I assume it's the 5-HT2A receptor, important for the actions of hallucinogenic phenethylamines and tryptamines, which fits with the name of the group considering the common use of such substances in plant form in rituals of many cultures.

The program they used for this, called ProteinMusic, is available as a free download. I got the program and tried some random gene sequences, making sure to trim off any bases before the start codon (ProteinMusic doesn't do this automatically). The program went straight through the stop codon at the end of the transcript, calling it "Z". I could not hear any difference in the sound between the actual polypeptide and the 3' UTR. The poly(A) tail was easy to recognize because of its repetitiveness, but that's about it. Someone commented that

"It may be possible for somebody who has heard the pattern of a calcium-binding site or an enzyme active site to recognize its occurrence in a novel protein."

Yeah right. I doubt 1% of bioinformatics scientists could identify the seven transmembrane helices in that serotonin receptor by ear, something that is typically easy to do by eye using hydropathy plots. This isn't to say that the idea of turning DNA sequences into music isn't neat in a purely fun sense, just that it doesn't do anything for science except maybe increase popularity.

Tuesday, July 18, 2006

The Rhymes of Molecular Biology-Part III

Just today I searched for MC Coffee Mug on iTunes, and The Thesis up for sale. I recommend for any scientists who like rap to check out this album. I don't think there is any other music like it out there.