Saturday, June 27, 2009

Ridiculous Fellows: Amazing Organ Performance

"Ridiculous Fellows," from Prokofiev's "The Love for Three Oranges" orchestral suite. Qi Zhang playing a Yamaha Electone Stagea, which she programmed herself.

Friday, June 19, 2009

Quorum-Sensing Molecules

I was fascinated by Bonnie Brasler's TED talk on Quorum-Sensing, and being a chemist I wanted to know more about the molecules involved. She did put up a slide with structures during the talk, but I wanted more so I did a search on PubMed and found this Perspective written by Brassler and Michael Federle.
My only experience with the notion of a “quorum” is our Faculty Assembly where we sometimes have difficulty achieving a quorum. In order for the meeting to be “official” and for any votes taken to be valid we need to have a minimum number of faculty present, a “quorum.” For bacteria, quorum sensing is the way the bacteria “count” one another. The bacterium releases a particular molecule, called an autoinducer - if there are lots of the molecules, then there are a lot of bacteria. If there are very few autoinducer molecules, then there are few bacteria present. The bacteria has a protein receptor that binds to the autoinducer molecule – so the bacteria can “sense” the presence or absence of autoinducer molecules depending on whether or not the receptor protein has detected any. In this way the bacteria can change their behavior depending on the number of bacteria present, as measured by the number of autoinducer molecules it finds. As a group, the bacteria behave one way when there is a low density of bacteria present and a different way when there is a high density of bacteria present.
In the simplest examples, quorum-sensing allows the bacteria to switch between two different behaviors depending on the number of bacteria present. One example would be the staphylococcus aureus bacteria – at low density they adhere to the surface of the cells of the host organism where they can grow and produce more bacteria. Once they reach a “quorum” there are enough bacteria present to be able to invade the host cells Their metabolism then shifts from producing the proteins that allow attachment to the outside of host cells and starts to produce proteins and toxins that allow the bacteria to enter the host cells. The light-producing bacteria from Bonnie Brassler's TED talk produce light when there are a lot of bacteria present, and stop producing light when there are few bacteria present.
Enough about biology, what about the molecules involved? In this Perspective, two categories of autoinducers are discussed, and one “special case.” Gram negative bacteria produce a type of autoinducer referred to as AHL for Acyl Homocysteine Lactone. Different types of bacteria will have different acyl groups attached to the homocysteine, and only recognize their own type of AHL. Gram positive bacteria do not use AHL's, instead they produce specialized proteins called AIP for AutoInducing Peptides, which consist of a string of 5 to 17 amino acids, some of which may be modified. The two types of autoinducer (AI) are detected by the bacteria when the AI binds to a receptor molecule in the bacteria. The details differ, but when enough AI's are around to bind to their receptors, the receptor causes a change in gene expression in the bacteria, which leads to a different behavior by the bacteria. 

The AHL's and AIP's are species specific: each type of bacteria produces only one AI and only recognizes it's own AI. The third type of molecule discussed is an unusual boron-containing molecule that may have a role for communication between different species of bacteria. The light-producing bacterium vibrio harveyi produces two different autoinducer molecules. The first is referred to as AI-1. AI-1 is an AHL molecule used for communication only among the V. harveyi bacteria. The other autoinducer is AI-2 which, on the other hand, may have a role in allowing different species of bacteria to communicate with one another.

AI-2 is synthesized by the bacteria in three steps from S-adenosyl methionine. The enzyme for the final step in this synthesis is called LuxS and as it turns out the gene for LuxS is found in many different bacteria, which all seem to both make and respond to the presence of AI-2. The implication of this is that perhaps AI-2 serves as some sort of generic autoinducer that allows bacteria to sense not only their own species, but also all other species of bacteria that produce AI-2.
The really interesting thing is that if we understand how bacteria communicate, we can find ways to short-circuit that communication. Many pathogens use quorum-sensing to regulate their virulence. In the example I mentioned earlier about S. aureus, the bacteria depend on reaching a “quorum” before they begin to “invade” the host cells. If their ability to sense one another is prevented, then perhaps their ability to invade the host and cause disease could be reduced.

Federle, M. (2003). Interspecies communication in bacteria Journal of Clinical Investigation, 112 (9), 1291-1299 DOI: 10.1172/jci200320195

Saturday, June 13, 2009

Cosmetic Toxicity Database

Wouldn't you like to know what's in the products you put on your skin? Skin Deep is an online database that brings together safety information on the ingredients in a wide variety cosmetics. They pull their information from many sources, including US EPA, EU, Canadian government, and a number that look like they are probably public interest groups.

You can search by product name, product category, manufacturer, or ingredient. All ingredients in the product are listed along with a safety rating of 0-10 and what type of hazard may caused by the ingredient, as well as a “Data Gap” which indicates the lack of safety information on the ingredient as a percent.

Of course, toxicity is a complex issue and not simple to nail down precisely. It depends on the dosage and the route of exposure (skin, oral ingestion, inhalation, etc). It would be nice to see the actual test data that they used to develop their ratings. Many ingredients are listed as (possible) carcinogens or as neurotoxins, but I can't tell how this was determined. If the actual test were based on oral ingestion or whole cell screens they may not be very informative about how the compound would behave when applied to the skin.

The other problem is dosage – most of the compounds in a cosmetic are likely to be found in small amounts – were the tests done with low concentrations to accurately reflect the “dosage” in a cosmetic? The pigments in particular seem to get the higher toxicity ratings – the thing about pigments is that it only takes a small amount of pigment to get a significant color. It may be difficult to measure the behavior of really small amounts accurately, higher dosages would be easier to measure but may not be good indications of the effects when exposed to only small amounts.

Particularly telling is the “Data Gap” rating which is "is a measure of how much is unknown about an ingredient. " A search for a common shampoo listed one of the ingredients as "Fragrance," which was given a hazard score of 8 (out of 10) with concerns about "Neurotoxicity, Allergies/immunotoxicity, Miscellaneous " and a Data Gap of 100%. The Data Gap score suggests to me that their toxicity rating is a not at all reliable. Most fragrances in commercial products are fairly simple compounds of a floral nature, and probably only present in a fairly small concentration. Although allergy concerns are probably sensible, I really doubt that washing my hair with shampoo is much of a risk for neurotoxic or immunotoxic side effects. Most people with a little common sense would probably tell you the same thing.

Skin Deep is probably a good place to start looking for information about the substances found in cosmetic products, but I don't know how much you should really trust the toxicity ratings that are given.

via BoingBoing

Wednesday, June 10, 2009

Too Funny: Roche xCELLigence Rock Video

I saw an ad for this in Science a while back. Cell Biology isn't my area, so I'm not too sure what xCELLigence IS, but the music video is entertaining.

They also have a Rock Ballad video.

Roche xCELLigence Rock Video

Tuesday, June 9, 2009

Bendable Crystals

Crystals are generally rigid and brittle, but this paper describes microcrystals of dimethylamino trans azobenzene that bend into a semicircle when a light is shined on them. That the azobenzene molecule responds to light is no real surprize, but the fact that the whole crystal changes shape, and reversibly to boot, was pretty cool.

Take a look at the video's of this that are provided, for free, in the supplemental information for the paper. The movie 002 shows the bending motion most clearly. This crystal is about 0.5 mm by 0.28 mm and 0.005 mm thick, so it is really tiny. A larger crystal probably would not do this.

So what's going on? The N=N double bond can be in either the trans orientation or the cis orientation. The trans version is preferred - the cis version suffers from steric crowding as the two benzene rings bump into one another. By shining light with the proper wavelength on the molecule, you can convert the trans into the cis molecule. Turn off the light, and the molecule can revert back the the trans version.

The authors were able to confirm that when they shine light on their crystals they convert about 1% of the molecules from the trans form to the cis form. This was readily apparent in proton NMR, but evidence could also be seen in changes in the UV-vis spectrum and the melting point of the crystals. After turning off the light source, the molecules in the crystal return slowly to all-trans.

So, how does this cause the crystal to bend almost in half? It seems to have to do with the way the molecules arrange themselves in the crystal lattice. The trans molecules are flat and stack into a very regular herring-bone type of pattern. The cis molecules don't fit this pattern - in addition to the U-shape, the cis molecules have a twist in them to reduce some of the steric strain between the benzene rings. The twist make the molecules much bulkier than the flat trans form As a result the cis molecules don't fit into the crystal lattice and cause the unit cell to be longer than the unit cell for only the trans molecules.

When the light source converts some of the molecules to the cis form, the side of the crystal nearest the light source appears to expand - because of the larger unit cell of the cis molecules. The side of the crystal away from the light source does not experience this and stays the same size. To accommodate the expanding surface facing the light source, the whole crystal bends away from the light source. When the light is turned off, the cis molecules slowly revert to the (more stable) trans form and the crystal un-bends.

Koshima, H., Ojima, N., & Uchimoto, H. (2009). Mechanical Motion of Azobenzene Crystals upon Photoirradiation Journal of the American Chemical Society, 131 (20), 6890-6891 DOI: 10.1021/ja8098596

Visualizing Data in the AlloSphere

How do I get one of these?

Monday, June 8, 2009

Structure of a Viral Protein Coat

The June issue of Popular Science has an image of the 3D molecular structure of the protein capsid for the Penicillium stoloniferum virus (PsV-F). This is the protein outer shell of the virus that acts as a container for the genetic information of the virus. The image doesn't appear to be on the Popular Science web site, so I went looking for the protein structure at the Protein Databank.

The image above comes from the PDB entry for structure 3es5 which is the crystal structure of the dimeric capsid protein (CP). The image above shows the biological unit which consists of 60 copies of the CP dimer in a roughly spherical arrangement. In Atomic Structure Reveals the Unique Capsid Organization of a dsRNA Virus, Pan et. al. used electron cryomicroscopy to compute a 3D reconstruction of the entire 120-mer of the protein capsid. The image in PopSci and the images in the original paper are much cooler than the one above, but this gives you an idea of what it would look like.

If you can't find a copy of Popular Science, you can see the original article at PNAS or Pubmed Central in September, since PNAS makes articles available for free 6 months after print publication.

Sunday, June 7, 2009

More Fun with Mercury

See how to make solid Fishes, Turtles and Frogs out of Mercury. Pretty cool, but don't try this at home.

via BoingBoing

Friday, June 5, 2009

Hot Blues from the Homemade Jamz Blues Band

These kids are great! I first heard of them on NPR last summer - check out the profile from NPR including several clips. Today I learned that they have a new CD coming out on Monday.