Wednesday, May 11, 2005

Gone fishin'

Blogging will be very light until early June. I'm off in search of that elusive creature, Positus firmus.

Tuesday, May 10, 2005

Scott Adams and focal dystonia

The Washington Post has an article about Dilbert cartoonist Scott Adams. He has focal hand dystonia, a loss of fine control in one or more fingers. This condition occurs frequently in musicians or others who rely on fine movements over many years. As you can imagine, this kind of neurological disorder can be a professional catastrophe.

Focal hand dystonia may represent an error in motor learning in which the extensive training of the finger motions causes a paradoxical blurring of the control regions in the cortex which are responsible for fine motions. Basically movements of the misbehaving finger somehow become "associated" with other intents, so that the finger moves when you don't want it to. One newish therapy tries to break the association by having musicians move their dystonic fingers while the rest of their hand is immobilized.

Adams is using a digitizing tablet to make his drawings at a much larger scale. In the interview, he says it's working for him because he doesn't have to push down so hard, and the larger scale means different hand motions (and probably different muscle sequences) are involved. So he is basically avoiding triggering the onset.

A nice technical reference to epidemiology and therapies is here.

More suprising findings about DNA instability in neurons

This months' Nature Medicine has a news item about a mouse mutant with defects in its ability to repair DNA damage. Neurons in these mutant mice have severe genomic damage, and are targeted for apoptosis (active removal), which results in a greatly reduced cerebellum. But if the scientists also interfered with the apoptosis pathways, the resultant double mutant mice had fairly good cerebellum size and function, despite presumably harboring a whole zoo of neuronal DNA damage!

Nijmegen breakage syndrome (NBS) is a rare human disease characterized by sensitivity to radiation and predisposition to cancer. In addition, humans with NBS have microcephaly (a much reduced brain size) and occasionally are mentally retarded. The gene which is mutated in humans with NBS, called NBS1 (known as Nbn in mice), is needed to repair DNA damage.

Special "Knockout mice" which lack Nbn gene function only in the nervous system accumulate DNA damage in neurons. Their neurological defects in the cerebellum, for the first time, mimics defects seen in humans with NBS. Scientists investigating these mutant mice found evidence for activation of the apoptosis pathway , which is used to remove injured or excess cells.

The big suprise, for me, came when the scientists introduced an additional mutation in the mice to remove function of the important apoptosis protein p53 (made by the gene Trp53). In mice which had mutations in both genes, the neurological problems were strongly reduced relative to mice lacking only Nbn function! Even Nbn mutant mice who additionally had only lost one functional copy of Trp53 still did better than the mice with both Trp53 copies normal.

The authors are at pains to emphasize that the double mutant mice are not normal. (In fact, the mice develop tumors and die young, because Trp53 is also important for tumor supression in the rest of the body. Thus the mice do not live long enough to evaluate how well their brains function into old age.) To underscore this point, it would have been nice to demonstrate aneuploidy or chromosomal damage in surviving double mutant neurons. Futhermore, the authors review the strong evidence that neurons in normal mice do undergo apoptosis throughout life. Thus the mice may have developed cerebellar problems later. Still, to have one devastating mutation ameliorate the effects of another seems a bit like stopping a bullet with a bullet.

While I could foresee that disabling the apoptosis pathway would lead to survival of cells that would normally be culled, I am just astonished that neurons with this sort of DNA damage would contribute anything at all to brain function. The double mutant mice are able to walk along a narrow rod (very easy for normal mice, but I wouldn't want to try) and could scurry along with the best of them, while their single mutant siblings had severe ataxia. Amazing.

Monday, May 09, 2005

Audience feedback for professors

ABC news ran a story last week about lecture halls equipped with clickers similar to the voting devices used on reality shows. Now professors can tell who's listening, and if their lectures are confusing or not.


Although I would take great pleasure to inflict my exact opinions on some of my undergrad lecturers (Query: how do you go lower than zero?), now that my turn to stand up there and drone is coming, maybe I wouldn't want to know....In the end, I think this info would actually be helpful.

Off by 50

Via ScienceNewsBlog , the mark of the beast was not originally 666. A 3rd century papyrus scrap (click on the link to see it) from the Oxyrhynchus digs show that an early copy of the Book of Revelation actually held it to be 616 .

The second link explains a bit more about the Greek numerology of the book of the Apocalypse. In Revelation, contemporary political figures being criticized were given a number as a moniker. 616 might refer to Emperor Nero, although there is still some disagreement. .

Far too much information on this topic is available at Wikipedia , which has already been updated to mention the Oxyrhynchus press release.

Friday, May 06, 2005

Art of science photography competition

Via Doug Tygar , the art of science photography winners are up over at Princeton. I really don't want to steal props from anyone by cutting and pasting images, but wow. At least look at this one. .

Ok, one more- look at this one.
another beauty.

Makes your car exhaust lemony fresh

Nature is reporting that a wash of citric acid can recharge catalytic converters. Catalytic converters are basically big arrays of platinum, which catalyzes the conversion of unburnt fuel and/or carbon monoxide to carbon dioxide. The problem is that other fuel components, like phosphorous and sulfur, eventually gum up the surface. And current cleaners are just too harsh, and pit the platinum surface. Is this sounding like a kitchen commercial yet?

So yes, citric acid seems to strip off the sulfur deposits and leave the platinum working like new. You have to cycle the exhaust line at 80 Celsius for a couple of hours.

Right now this is still more expensive for the average user than just replacing the thing.

Thursday, May 05, 2005

The color of life

Astrobiologists would like to find life on other planets even if it's impractical to actually go there. At , Seager et al. suggest that a planet with photosynthetic organisms should show a spectral abnormality. That is, the "plants" are harvesting lots of solar energy in some wavelengths, and rejecting other wavelenghths, which creates a distortion in the spectrum of light returning from the surface.

In the case of Earth's chlorophyll , people on Earth see lots of reflected green; but the diagnostic signal from outer space would actually be a sharp "edge" in the red wavelengths:


Earth plants use UV and bluish light for photosynthesis, and chlorophyll also absorbs far-red light. The high reflectance in the rest of the visible spectrum is thought to be an adaptation to prevent overheating. The result in this case is the sharp "red edge" between reflectance and strong absorption between 750 and 700 nm.

So my first thought was that the position of such a spectral edge is going to depend quite a lot on the exact chemistry of the chlorophyll equivalent; which in turn would probably have been fine-tuned via evolution to match whatever star's spectral output. Well, they're way ahead of me. I didn't realize this but people have been giving extraterrestrial photosynthesis quite a lot of thought, and the spectrum harvested by chlorophyll would also be useful for other earth-like planets. The main exception is a cool sun (reddish?) in which case you'd need a two-photon capture photosynthesis... you're best off reading the web page attachments! In any case, it looks like there are some universal constraints keeping the visible light reflectance high and therefore yielding a red edge.

To really nail it, you have to look for "seasonal" changes in this signature.

My own opinion is that you'd expect "chemical-eater" strategies to be easier, so that photosynthesis might only be in fewer places. However, I guarantee you that if there is enough plant life to sense remotely, there will for sure be plant-eaters, and carnivores too.

UPDATE: An older reference to this concept is here.

UPDATE, June'05: The "red edge" is expected to be harder to see on a planet dominated by waterborne slimes such as algae etc. The need to reflect thermal energy would be a lot less for water dwellers.

Tangled Bank is up

The Tangled Bank carnival of science-related blogging is up over at Buridan's Ass . It's a fantastic writeup, with a big selection!

Wednesday, May 04, 2005

Your cappucino has no froth

Metafilter links to a hilarious Women's complaint against coffee, in which the demon bean interferes with men's spousal perfomance.

water, and murmur insignificant notes till half a dozen of
them out-babble an equal number of us at a Gossipping...

...Thus like Tennis Balls between
between the Coffee-house and Tavern, whilst we poor Souls sit mopeing all
alone till Twelve at night, and when at last they come to bed smoakt like a
shotten Herring or a dryed Bulrush; which forces us to take up this
Lamentation and sing

Much more in the comments section.

UPDATE: I started to think it was a hoax, because the Metafilter link was to an unadorned html, and because the final, legal petition, portion of the document was in no way as ornate and overblown as the preamble (even as a hoax, that preamble would be a masterpiece!). Also, I had some, ahem, reservations about the physiological premise of the complaint. Even after big night at Starbuck's, I like to think I'm still a bit more Comfort than a shotten Herring (although, sadly, I do indeed babble like a Frog in a puddle).

I followed the story backwards through several links from a Livejournal, to Scribbling Woman (awesome blog!), to Irwin Primer at the C18-L listserve . This last person seems to have known the document from before; and his link points back to the same html which Metafilter references. So I guess it is real. It's really nice to see everyone preserving the chain of links.

Final word belongs to Jim Chevalier also at the C18-L listserve, who says that coffee was also associated with impotence in France.

Tuesday, May 03, 2005

Bill Gates wants to build cars that won't crash

This is almost too funny to believe. Bill Gates envisions cars that won't crash. Uh, Bill?

In case you had ANY desire to entrust your life to a Microsoft automobile, here is an old retort from General Motors to an earlier statement of Bill Gates:

2. Occasionally your car would die on the freeway for no reason, and you would just accept this, restart the car and drive on.
3. Occasionally, executing a maneuver would cause your car to stop and fail and you would have to reinstall the whole engine. For some strange reason, you would accept this too.

As they say, read the whole thing.

Water flow on Mars

From the Mars Today page, this beautiful picture of a meandering water channel at the base of a ridgeline. The interpretation on the Mars Today page says that the water must have been released multiple times over a long period, as the main channel and some craters show visible subsequent erosion. If you want to see evidence of life, you'd want to be turning rocks over right here in the base of the arroyo for biofilm fossils.
Also, the European mars orbiter will begin unfurling its radar booms over the next two weeks. This maneuver had been delayed for more than a year because of fears that it would damage other instruments. The ground-penetrating radar will allow the orbiter to detect subsurface water.

My eyes always optically invert these grayscale images, so that my first perception on seeing the craters is always to see little humps. I guess it should be random which percept comes first, "inny" or "outy" but I do it 100% wrong.

Waterflow on mars">

Aneuploid neurons- they're in your right mind.

I have blogged before about chromosomal changes in normal brain cells. Normally every cell in your body has the same number of chromosomes, and cases of too few or too many chromosomes (conditions collectively called aneuploidy) can damage the way the cell functions. Scientists who were looking in human brains for copy numbers of chromosome 21 (trisomy of chromosome 21 causes Down's syndrome, which results in cognitive defects) discovered that an appreciable fraction, about 4-5%, of normal human brain cells were aneuploid for this chromosome. They could even identify some cases of cells carrying four copies.
Other work from the same lab had identified mutant mice with greatly elevated numbers of aneuploid cells. The mutations affected the apoptosis pathway, which is responsible for eliminating certain damaged or excess cells. This suggested that aneuploid cells seen in normal brains had escaped a removal process responsible for clearing away most of the others.

Work by Kingsbury et al. in last week's PNAS reports some additional observations about this phenomenon. They wanted to know whether aneuploid cells were neurons, or if they were exclusively nonneuronal. In addition, since the mouse mutant work suggested that aneuploid cells are actively removed, they wanted to know whether the aneuploid cells were neurons in good standing, with functional connections and with regular activity patterns.

Kingsbury et al. tackled the question of neuronal identity and proper connections simultaneously. Since neurons are the only brain cells which make long-distance connections (an introduction to the parts of a neuron is here ), they used a retrograde tracer, a compound which neurons take up from their synapses and transport back (even over long distances) to their cell body. Kingsbury et al. then looked for aneuploid nuclei sitting inside a cell body which was positive for the tracer, thus identifying cells which were aneuploid plus connected. To score for aneuploidy, they used male mice (XY) and looked for cells with more than one copy of X or more than one Y.

They were able to find many such neurons, and in addition they found that different areas of the cortex had different percentages of retrogradely labelled aneuploid neurons. Overall, extra copies of either X or Y were present in about 20% of all the neurons with tracer. (This is much higher than the 5% estimated from the chromosome 21 experiments. In the discussion, Kingsbury et al. cite an estimate of 64% of brain cells with some deviation from normal karyotype.)

To check the activity of the aneuploid neurons, they used immunostaining against two proteins, Egr and c-fos, which are strongly expressed in neurons which have recently been active. (An technical reference to this concept is here. )This ended up being a triple-label experiment, for FluoroGold (connectivity/neuron identity); X or Y aneuploidy; and immunoreactivity. This is an amazing technical accomplishment. Their results in this case are limited to just a few positive observations, including one case in which they stimulated olfactory system activity by presenting the male with a novel smell. I do wish they had pursued this line of experiments a bit farther, to give an estimate of the relative percentages of activation of aneuploid connecting cells versus activation of all. Again, since the apoptosis pathway is apparently actively removing aneuploid brain cells, the activity of aneuploid neurons is an important measure of their health.

What really suprises me about this work is that I would have thought neurons would have stringent DNA requirements for correct function. I like to think of neurons as having the most complicated job to do of any cell, which in turn led me to presume that neurons need intact DNA much more than, say, a skin cell. I guess this presumption is trumped by the general robustness of evolved systems against defects. Neurons might be escaping the "chromosome counter" because they never divide again. Aneuploidy in cells that will never divide is less of a risk to the animal than aneuploidy in, say, a stem cell, that gives rise to many copies, some of which may acquire additional chromosomal defects.

Sunday, May 01, 2005

Boilerplate science over at Scientific American

There's no need for me to keep blogging, because the The SciAm Editor's blog knows a better way. The Onion will do my science writing for me.

Google to change search strategy




