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Economics 101

Monday, December 31, 2007

I'm going to broaden the focus here with a lesson in elementary economics. This is a fairly standard example used by economists everywhere, to illustrate how competitors position themselves to divide up a market.

Suppose there is a nice beach somewhere. (It may be either swimsuit optional, or else the gov't requires all users to wear suits, because the gov't knows what's best for everyone. However, that's not germane to what follows.)

Suppose further that two hot dog vendors want to locate their carts on the beach in order to maximize their revenue. You might think that the best way to do this is to imagine the beach divided in half, with each vendor in the middle of one half. That places one 1/4 of the way from one end, and the other 1/4 of the way from the other end. Assuming people are uniformly distributed on the beach, this minimizes the maximum distance a customer needs to walk in order to get a hot dog – at most 1/4 the length of the beach.

But counterintuitively, either vendor can apparently do better by moving to the middle of the beach. That way the vendor who moves to the middle first can still have all of his previous customers, plus half the customers between the center of the beach and the other vendor. Unfortunately, if the other vendor moves to the center also, to avoid losing business, the total quantity of hot dogs sold will be less for both than previously. This is because about half of the customers would have to walk farther to get a sausage, and many of these won't want to get so much exercise.

Actually, however, this only illustrates how hypothetical a lot of reasoning by economists is. What "should" happen if markets were efficient (which they aren't) is that after both existing vendors have moved to the center, then somebody with a little capital would buy new carts, hire two undocumented immigrants (at less than minimum wages), and set them up in the old .25/.75 points.

This could go on indefinitely, until the "point of diminishing returns" when the market for hot dogs on the beach is "saturated".

But at that point, someone with even more capital would step in with an advertising campaign to promote eating hot dogs to beach-goers, and then set up additional carts, selling hot dogs made from recycled turkey parts at prices below cost, to drive all the other vendors out of business. Then the last entrant can buy up the remaining assets in bankruptcy, cut back on the number of locations, but not raise the product quality, and make more money than everyone in total previously.

Maybe, just maybe, the beach-goers would demand gov't regulation of hot dog vendors at that point. But the remaining vendor can use his substantial profits to buy off any relevant gov't officials and fix any elections that might be held (using his electronic voting machine subsidiary), to prevent any gov't action.

And then, using this new gov't-relations infrastructure, the vendor would lobby for gov't subsidies to help produce lower-cost hot dogs. The gov't would oblige (since many officials are former vendor executives) and hold secret meetings to plan the subsidies and make all necessary arrangements. Mainstream media (large portions of which are owned by friends and suppliers of the vendor) would laud the gov't for its foresight. Some sharp lawyers might challenge such practices in court, but since a majority of judges have been appointed by the gov't on the advice of its lobbyists, the lawsuits would go nowhere. Further lawsuits would be forestalled by "tort reform".

And "consumers" would go on obliviously, happily eating hot dogs until they (the "consumers") keel over from cardiovascular disease, due to bad diet and lack of exercise. The only mistake made by the vendor and his allies in all this is failing to secure gov't health care to keep the "consumers" alive a little longer. Because "economists" had forecast that such a move would not actually improve profits in the long run, since older "consumers" would be too sick to eat many hot dogs.

Wealthy preachers of religion would then step in to assure the populace that all of this was God's plan, and remind all the survivors that there was still time to contribute to the church's building fund, before the Rapture.

Happy New Year!

Update (1/12/08): At a link to this post, the writer comments that governments and other powerful actors have long intervened in economic affairs. The example cited involves medieval cartels and monopolies, but of course this goes back much farther in history – as long as any sort of gov't has existed, I would suppose.

And in case anyone thinks this note is a little over the top in parodying economics, here's something I came across just a few days after writing the above. It's by economist and hedge fund manager Jean Paul Schmetz:
In my field (theoretical economics), I believe that most ideas taught in economics 101 will be proved false eventually. Most of them would already have been officially defined as false in any other more hard-science, but, because of lack of better hypotheses they are still widely accepted and used in economics and general commentary. Eventually, someone will come up with another type of hypotheses explaining (and predicting) the economic reality in a way that will render most existing economics beliefs false.

Physical sciences news, 12/17/07-12/23/07

Sunday, December 23, 2007

Gamma-ray bursts
There are several types of gamma-ray events that go under the name of "gamma-ray bursts", but the two main categories are "long" and "short" – referring to the duration of the burst. Long bursts have been generally attributed to very energetic supernovae that direct most of their energy into a narrow beam, which just happens to be visible from Earth. But most powerful supernovae are due to the collapse of a very large, young star – normally found only inside galaxies. So the detection of a long gamma-ray burst outside of any visible galaxy is rather a surprise. On the other hand, short gamma-ray bursts have been suspected to result from the merger of black holes and/or neurton stars. So another surprise is that the LIGO gravitational wave detector did not register any such event in connection with a recent short gamma-ray burst event.

Intergalactic 'Shot In The Dark' Shocks Astronomers
Cosmic explosion detonates in empty space
A Gamma-Ray Burst Out of Nowhere
Baffling Cosmic Explosion Comes Out of Nowhere
Cosmic explosion is shot in the dark
LIGO Sheds Light on Cosmic Event

Supernova remnants
It has generally been supposed that most elements heavier than hydrogen and helium that are not still locked up inside stars were formed in very massive stars that became supernovae and scattered most of their material into space. But actual traces of such "dust" in the vicinity of known supernova remnants have not been confirmed – until now.

10,000 Earths' Worth Of Fresh Dust Found Near Star Explosion
Litterbugs of the Universe Busted
Freshly Formed Dust in the Cassiopeia A Supernova Remnant as Revealed by the Spitzer Space Telescope

Very early star formation
Given that interstellar dust contained within galaxies is the result of supernovae explosions of previous generations of massive stars (see above), it is surprising that a galaxy seen as it was only 1.5 billions years after the big bang exhibits a very high rate of star formation (1000 times what now occurs in the Milky Way), and in a very dusty environment besides. But that's exactly what the galaxy GOODS 850-5 seems to show.

New View of Distant Galaxy Reveals Furious Star Formation
Galaxy Has 1,000 Times Our Rate of Star Formation
GOODS 850-5 -- A z>4 Galaxy Discovered in the Submillimeter?

Cosmic inflation
Although the cosmic microwave background (CMB) represents an image of the universe at about 380,000 years after the big bang, some very subtle details of the variation in temperature of the CMB from point to point contain information about the very earliest instants of the universe. (Like time t=10-35 sec, to be more precise.) It has been expected that a very careful analysis of the data will tell us something about the hypothesized phenomenon of cosmic inflation. The latest analysis claims to rule out the simplest model of inflation. However, it may be that the data obtained in the WMAP mission is insufficiently detailed for a satisfactory resolution of this issue, and we'll have to wait for a more sensitive measurement from the forthcoming Planck mission.

No Dice for Slow Roll?
Detection of primordial non-Gaussianity (fNL) in the WMAP 3-year data at above 99.5% confidence
Detection of primordial non-Gaussianity (fNL) in the WMAP 3-year data at above 99.5% confidence

Data gathered from many years of surveillance of Mars by satellite missions and landers provides strong indications that Mars was warm and wet early in its history. Yet evidence of the most likely greenhouse gas, CO2, that could have sustained a warm, wet environment has been conspicuously absent. The evidence now points to a different greenhouse gas, SO2, instead. But early history aside, it now looks as though Mars could have an active (water ice) glacier at the present time.

Sulfur dioxide may have helped maintain a warm early Mars
Fire and Brimstone Helped Form Mars Oceans
Possible solution to Mars enigma
Maybe Sulfur Dioxide, Not Carbon Dioxide, Kept Mars Warm
Greenhouse clue to water on Mars
How Mars Could Have Been Warm And Wet But Limestone Free
Red Planet Still Packs Surprises
'Active glacier found' on Mars
Red Planet Appears to Host Active Glacier

Extrasolar planets
How much technology would be required to learn something about the surface conditions (e. g. continents, oceans, clouds) on extrasolar planets in our neighborhood? New calculations based on plausible strategies for observing such features suggest... not a whole lot more technology than we will soon have. So if there are any civilizations at least as advanced as our own on any of those planets, they probably already have a fair idea of what Earth is like.

Alien astronomers could discern Earth's features
To curious aliens, Earth would stand out as living planet
MIT Asks: How Would Extraterrestrial Astronomers Study Earth?

Sea level rise
A rise in sea levels is one of the most troublesome effects expected from global warming over the next several hundred years, but it has been difficult to make a good estimate of how quickly this would happen. However, about 124,000 years ago the planet was on average about 2° C warmer than it is now – and what it may be in just 100 years. New research claims to show that sea levels then were rising at a rate of 1.5 meters per century – about twice the current "consensus" forecast for our own times.

Study suggests future sea-level rises may be even higher than predicted
Rising seas 'to beat predictions'
Lessons From an Interglacial Past
Fast-Rising Sea Levels: An Interview on Research in the Red Seas

FoxO transcription factors

Transcription factors are proteins that help regulate genes. This regulation may involve either enabling the expression of a gene or preventing expression. In the first case, the transcription factor is an "activator", and in the second case a "repressor".

Transcription factors perform their function by binding to a particular portion of DNA that is specific to a given gene. When bound to the appropriate DNA segment, a transcription factor affects gene expression by either facilitating (activator) or inhibiting (repressor) the operation of RNA polymerase in transcribing the affected gene into messenger RNA. Usually more than one transcription factor must be present to affect gene transcription, and additional proteins (called "cofactors") may also be required.

To make things even more interesting, transcription factors usually affect multiple genes, which may be otherwise unrelated to each other.

A particularly important family of related transcriptions factors comprises what are called "forkhead box" proteins, or Fox proteins, for short. (The name refers to a sequence of 80 to 100 amino acids that are part of the protein and bind to DNA, and which was originally discovered in fruit flies (Drosophila).)

Among the genes that Fox proteins are involved with are genes related to cell growth, proliferation, differentiation, longevity, and embryonic development. So there are Fox proteins that are important for things like cancer and stem cells – and thus it's quite useful to know about them.

An important subfamily of Fox proteins are the FoxO proteins, and we'll discuss some recent examples in this note.

To begin with, perhaps the most recent example is this:

Molecular Signal That Helps Muscle Regenerate Discovered (12/19/07)
Muscle regeneration after injury is complex and requires a coordinated interplay between many different processes. Key players in regeneration are muscle stem cells, so-called satellite cells. They divide and produce many new muscle cells to fix the damage incurred by injury. A crucial regulator of muscle function and repair is a signalling molecule called calcineurin. It is activated by injury and controls the activity of other key proteins involved in differentiation and the response to damage.

It turns out that calcineurin works by inhibiting FoxO.
Using sophisticated molecular techniques, the scientists revealed that calcineurin accomplishes its effect on muscle by inhibiting another protein called FoxO. FoxO is a transcription factor, a protein that plays a crucial role in skeletal muscle atrophy through the induction of genes involved in cell cycle repression and protein degradation. Suppressing the effects of FoxO, calcineurin ensures that proliferating cells stay alive and keep dividing to produce enough cells to repair muscle damage.

In this case, the normal function of FoxO is to inhibit cell proliferation (as a check on cancer), but this needs to be bypassed (temporarily) to enable muscle regeneration.

This result follows the discovery a few months earlier of the way a specific FoxO protein (FoxO1) cooperates with another important developmental protein (Notch) to control muscle cell differentiation:

Building Muscle Requires Foxo1 (8/25/07)
The mechanisms by which Foxo proteins regulate metabolism are relatively well characterized. However, little was known about the mechanisms by which these same proteins regulate cellular differentiation.

New data generated by Domenico Accili and colleagues at Columbia University, New York, now indicates that Foxo1 cooperates with Notch to control muscle cell differentiation in vitro.

Overexpression of either a constitutively active form of Foxo1 or a constitutively active form of Notch was found to inhibit the in vitro differentiation of a mouse myoblast cell line.

Note that the preceding alludes to the involvement of FoxO proteins in regulation of metabolism. This comes about because they affect the insulin signaling pathway, and hence also glucose and lipid metabolism.

This function is what allows yet another well-known protein, mTOR, to play a role in "metabolic syndrome" – a group of disorders that includes insulin resistance, heart disease and high lipid levels. (mTOR is short for "mammalian target of rapamycin". It's a protein kinase that modifies other proteins by phosphorylation.) The same mechanism appears relevant also to the "Atkins diet" and the effects of calorie restriction.

Fly Genetics Reveal Key Workings Of Atkins Diet (8/8/06)
Using fruit flies bred with a newly created mutant form of the gene TOR (short for target of rapamycin), Oldham and his colleagues were able to determine how the TOR pathway interacted with other important regulators of insulin, glucose and lipid metabolism.

TOR is an ancient gene, found in nearly all animal and plant cells. The researchers discovered that their new mutant fly reduced TOR function, allowing them to observe what happens when TOR's influence is removed.

Reductions in TOR function lowered glucose and lipid levels in the body. They also blocked the function of another important insulin regulator, a factor called FOXO, which is known to be a critical mediator of insulin signals and therefore glucose and lipid metabolism.

As if all that weren't enough, FoxO proteins are also involved with cancer and stem cells:

Gene Knockouts Reveal FoxOs' Vital Functions In Cancer Defense, Health Of Stem Cells (1/25/07)
In an elegant, multiple-gene knockout experiment, a team of Boston scientists has discovered that a trio of molecules, called FoxOs, are fundamentally critical in preventing some cancers, maintaining blood vessel stability, and in keeping blood-forming stem cells healthy. ...

The researchers at Brigham and Women's found that mice engineered to lack genes for the FoxO1, FoxO3, and FoxO4 molecules had serious blood abnormalities. Without the FoxO gene-regulating molecules, the rodents' blood stem cells -- master cells that give birth to working blood cells while also renewing themselves -- divided too fast and "burned out." ...

In the companion paper, lead author Ji-Hye Paik, PhD, of Dana-Farber and colleagues from the DePinho lab report that the three FoxO molecules, known as transcription factors, normally function as tumor suppressors that override maverick cells threatening to grow too fast and form tumors. When FoxOs are eliminated, it may allow cancer to develop.

And even that's not the end of it. FoxO proteins are also involved in the increased levels of inflammation often associated with the aging process. (This phenomenon has been tagged with the neologism "inflammaging".) It has been hypothesized that inflammaging results from the effect of phosphorylated FoxO on another notorious transcription factor, NF-κB (which is heavily involved in inflammation). Some of the effects of calorie restriction may also be due to FOXO phosphorylation. Reference: Restricting inflammaging (11/12/07)

FoxO is also regulated (as is P53) by SIRT1 – so this is yet another relationship to calorie restriction. Reference: Unlocking the Secrets of Longevity Genes

Additional references (for the seriously interested):

An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.

Ageing: When Less Is More

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Physical sciences news, 12/10/07-12/16/07

Sunday, December 16, 2007

Milky Way
Stars occupying regions above and below the disk of a spiral galaxy like the Milky Way are said to be in the galaxy's halo. In our own galaxy it turns out that there are two distinct halo regions, and they are rotating in opposite directions.

Milky Way's two stellar halos have opposing spins
Discovery shows Milky Way halo is split in two
Huge Newfound Part of Milky Way Rotates Backward

Extrasolar planets
Some other solar systems besides ours undoubtedly have rocky planets like Mercury which always show the same face to the host star. A computer simulation shows that there could be a narrow potentially habitable region between the light and dark sides of such a planet.

'Twilight zones' on scorched planets could support life

Gliese 581d
Gliese 581d is a rocky planet recently discovered in orbit around the red dwarf star Gliese 581. It has about 8 times the mass of Earth. Two teams have now done simulations of the atmosphere of Gliese 581d and concluded that an atmosphere could exist and have properties considered necessary for Earthlike life to develop.

Gliese 581: one planet might indeed be habitable
Gliese 581d: A Habitable World After All?
Is Gliese 581 Habitable?
More Evidence that Gliese 581 Has Planets in the Habitable Zone

Haze on HD 189733b
HD 189733b is a gas giant extrasolar planet of the yellow dwarf star HD 189733 A. Although previous observations had suggested the presence of water vapor in the atmosphere, the latest set of observations using the Hubble Space Telescope did not find evidence of water, sodium, or potassium in the atmosphere. However, there was an indication that the atmosphere did contain a haze of dust particles of unknown composition about 1 micron in size.

Hazy red sunset on extrasolar planet
Dust in a Hot Jupiter's Atmosphere
First Sunset Outside Our Solar System Glimpsed
A Red Haze on Distant Exoplanet
HD 189733b: A 'Murky' Extrasolar Planet
The sunset on HD 189733b

Silica and the possibility of life on Mars
One of NASA's Mars rovers has found what appears to be a a deposit consisting largely of silica (SiO2) – very fine grained beach sand, essentially. On Earth such deposits are found only in certain hot springs or volcanic fumaroles. Here both such environments support a great deal of microbial life. If life ever existed on Mars, it would likewise probably have thrived in such an environment.

Clues to a Steamy Martian Past
Mars Rover Investigates Signs of Steamy Martian Past
Mars robot unearths microbe clue
Mars Rover Finding Suggests Once Habitable Environment
Mars rover finds signs of microbial life
Spirit's Big Discovery
Mars Rovers Find New Evidence Of 'Habitable Niche'

Organic compounds on Martian meteorite ALH 84001
ALH 84001 is a meteorite whose composition indicates it crystallized from molten rock 4.5 billion years ago on Mars. Over 10 years ago a team of NASA scientists hypothesized that some very small (20-100 nm) structures in the meteorite might be traces of life, but the claim was quite controversial and is no longer widely accepted. However, a recent comparison of the meteorite with terrestrial rocks suggests that simple organic compounds found in ALH 84001 could have formed, as in their terrestrial counterparts, in a chemical process catalyzed by magnetite (Fe3O4).

Building blocks of life formed on Mars
Building Blocks of Life Formed on Early Mars?
Life's Building Blocks Found in Mars Rock
Allan Hills 84001 Analysis Confirms Building Blocks Of Life Also Formed On Mars
Building Blocks of Life Can Form on Cold, Rocky Planets — Anywhere
Martian Meteorite Harbors Life's Building Blocks

Saturn's rings
When Saturn's rings were first examined close-up by the Voyager missions in the 1970s, it was concluded that they had formed relatively recently (like 100 million years ago) when a moon of Saturn was destroyed in a collision with another moon or an asteroid. But the latest evidence from the Cassini mission indicates that Saturn may have had similar rings since the formation of the solar system 4.5 billion years ago. However, it appears that material in the rings is continually accreting into new moonlets, only to be destroyed again in later collisions.

Saturn's Rings May Be As Old As Solar System
Saturn's rings 'may live forever'
Saturn's Rings Older Than First Thought?
Saturn's Rings Could Be as Old as the Solar System
Saturn’s Rings More Ancient than First Thought
Saturn's Rings: Moon Remnants Or As Old As The Solar System?
Recycling keeps Saturn's rings youthful

Greenhouse gases
A new study indicates that human destruction of peat bogs may be responsible for emission of amounts of CO2 possibly 10% as much as all burning of fossil fuels. Another study proposes a new model, taking into account the role of nitrogen, of how carbon is recycled among plants, soils, and the atmosphere.

Peatland destruction is releasing vast amounts of CO2
New model revises estimates of terrestrial carbon dioxide uptake

Arctic ice
Some scientists who have studied the melting of Arctic ice now believe the ice could melt entirely in summer as soon as 2013, instead of 2040 as previously thought. Even this summer the melting has resulted in sea surface temperatures, in some places, 5° C above average – a level never before recorded. And this summer's melt of the Greenland ice sheet was 10% more than the previous record from 2005.

'The Arctic is screaming' — summer sea ice could be gone in five years
Arctic summers ice-free 'by 2013'
Without its insulating ice cap, Arctic surface waters warm to as much as 5 C above average
Greenland melt accelerating, according to CU-Boulder study

Near-record high temperatures
And overall, 2007 figures to be Earth's second-warmest year on record, while the past 10 years have been the warmest decade ever recorded.

2007 Brought Near-Record Heat
2007 data confirms warming trend
1998-2007 warmest decade, UN agency says at climate meet

P53, a versatile gene

Friday, December 14, 2007

P53 is well-known for its role in regulating the cell cycle so as to suspend the cycle or even lead to cell death via apoptosis in case damage to a cell's DNA is detected. This function is especially important in forestalling cancer.

And as we noted here, p53 is also involved with skin tanning.

But that's not all p53 is good for. It also plays a role in fertility, which has recently been reported by one of the co-discoverers (Arnold Levine) of p53:

Cancer Fighter May Be Fertility Helper
A protein known primarily for its role in fighting cancer also helps embryos implant in the womb, according to a study in mice. The find may explain why some women have difficulty becoming pregnant.

More information: here, here

But the list of p53's goodness doesn't stop there. It also slows aging, apart from deterring cancer, but via the same mechanism:

Anti-cancer gene p53 doubles up as anti-ageing agent
The latest research suggests that one of the genes that protects us from cancer may also help delay the ageing process.

A new study has found that a particular gene, p53 which has been previously linked to premature ageing, along with one of its cellular regulators, called Arf, may boost the body's antioxidant activity to keep cells younger longer and thereby slow down the aging process.

The regulatory chemical Arf, lets p53 know that a particular cell is in trouble and marked for elimination.

More information: here, here, here, here

But, surprisingly, at least in fruit flies, reducing p53 activity may also increase lifespan, and apparently in the same way that calorie restriction does:

Key To Longer Life (in Flies) Lies In Just 14 Brain Cells
Two years ago, Brown University researchers discovered something startling: Decrease the activity of the cancer-suppressing protein p53 and you can make fruit flies live significantly longer.

Now the same team reports an intriguing follow-up finding. The p53 protein, they found, may work its lifespan-extending magic in only 14 insulin-producing cells in the fly brain.

How was this connected with calorie restriction? Simply by noting that calorie restriction in fruit flies didn't increase longevity when p53 activity was suppressed in only 14 insulin-producing cells of the flies' brains:
Studies have shown that low-calorie diets can significantly increase the lifespan of flies, worms, mice and rats. The phenomenon is of intense interest to researchers who study aging. They want to know if caloric restriction works in people and if drugs could be made to mimic its effects.

So researchers restricted the diets of the flies and ran the same experiments. The calorie-restricted flies didn't live any longer when p53 was reduced in the insulin-producing cells. This evidence supports the notion that p53 reduction is one of the direct effects of caloric restriction.

Even more intriguing, Helfand said, is the fact that the 14 insulin-producing cells that seem to be critical for lifespan extension are the equivalent of beta cells in the human pancreas. Beta cells make and release insulin, the hormone that controls the level of glucose in the blood. The research team found that when p53 activity drops, so does insulin-responsive activity in the fat body, the major metabolic organ in the fruit fly.

The involvement of insulin in this effect is especially interesting, as insulin signaling has also been found to be involved in the mechanism by which sirtuin proteins extend longevity in nematodes and fruit flies (and perhaps other organisms).

One wonders just how p53 came to play such a prominent role in cellular processes. Some researchers think they have found the answer – endogenous retroviruses that have actually proven beneficial to the host genome:

Ancient Retroviruses Spurred Evolution Of Gene Regulatory Networks In Humans And Other Primates
Scientists have long wondered how a master regulator such as p53 gained the ability to turn on and off a broad range of other genes related to cell division, DNA repair, and programmed cell death. How did p53 build its complex and powerful empire, so to speak?

Using the tools of computational genomics, the UCSC team gathered compelling evidence that retroviruses helped out. ERVs jumped into new positions throughout the human genome and spread numerous copies of repetitive DNA sequences that allowed p53 to regulate many other genes, the team contends.

"This would have provided a mechanism to quickly establish a gene regulatory network in a very short evolutionary time frame," said Ting Wang, a post-doctoral researcher at UCSC and lead author of the paper.

It's hard to avoid a suspicion that there's a lot to the story of p53 left to be discovered.

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Ultra-high energy cosmic rays.

Monday, December 10, 2007

I'm just trying to catch up on interesting science news of the past few weeks, and what happens? I pick a topic that seems to have had significant new developments and is also straightforward enough for a relatively brief post. But instead of something I can do justice to with just a handful of links to good reports (so I don't need to do that much work), I find myself in a brier patch. Frustrating.

The general topics is cosmic rays. The phenomenon of radioactivity was discovered in 1896 by Henri Becquerel. At first the only known source of radioactivity was certain naturally occurring radioactive elements in the Earth itself. But in 1912 Victor Hess deduced that there must be another source of radioactivity outside the Earth's atmosphere. These came to be known as cosmic rays (as opposed to other kinds of "rays", such as X-rays, alpha rays, beta rays, and gamma rays, which have known terrestrial sources). Hess received a Nobel Prize in physics in 1936 for his discovery, indicating that by then scientists generally agreed the phenomenon was genuine, and interesting.

Given that, the next questions had to be: what do cosmic rays consist of, and how are they produced? Even today we are still in the process of answering those two questions, though we think the answers are pretty well known for all but the most energetic cosmic rays.

I'll discuss cases involving different energies in a moment, but first there are some basic distinctions. Now that we have spacecraft, we can in principle observe cosmic rays directly, though this hasn't actually been done systematically. (It turns out that the highest energy cosmic rays, which are still the least well understood, are too rare to be observable with non-terrestrial instruments of sufficient size.) At the Earth's surface we can't observe cosmic rays directly. Assuming cosmic rays are ordinary particles like electrons, protons, or atomic nuclei (and we've seen nothing to indicate otherwise), all we can see are showers of electrons and more exotic particles like muons. All the evidence indicates that these showers are the result of collisions between actual cosmic rays and molecules in the atmosphere.

There is an additional distinction that can be made between "primary" and "secondary" cosmic rays. Originally this distinction was between the particles we actually observe in showers ("secondary") and the ones ("primary") that cause the showers. The latter, of course, are the ones that need to be understood. But we now realize that the particles that enter our atmosphere may themselves be a result of collision between the "real" primary cosmic rays and other particles floating in interstellar space. Since we're concerned with what the particles are in their original form, it is those that are now usually called primary (or simply "cosmic rays" without further qualifiers), while everything else is secondary.

Obviously, the most important step in understanding (primary) cosmic rays is to figure out where they come from, and for that we would like to know the direction from which they enter our atmosphere. We know that some relatively low energy cosmic rays originate in the Sun ("solar cosmic rays"). Unfortunately, except for those and all but the most energetic other cosmic rays it is impossible to tell the direction they have come from. That's because the particles that could make up cosmic rays should have certain properties. Except for solar cosmic rays, the particles should be stable and not decay over time spans of (at least) many years. We can also rule out very light particles like neutrinos. Cosmic rays could be something totally exotic that's never been observed before, except in that case it's very likely they would not interact with ordinary matter – so they would not be capable of producing showers of secondary particles that we observe. Among particles currently known, then, that leaves only charged particles such as electrons, protons, and atomic nuclei.

However, unless a charged particle has extremely high energy, in excess of what has been observed for most (but not quite all) cosmic rays, its motion will be affected by our galaxy's magnetic fields, or even by the magnetic field of the Earth. We observe that almost all cosmic rays energetic enough not to be significantly affected by Earth's magnetic field appear to come from directions isotropically distributed over the sky. So we can't identify any particular spot from which most cosmic rays appear to originate, because our galaxy's magnetic fields have randomized their directions.

Very recent results strongly suggest that a few very rare cosmic rays ("ultra-high-energy cosmic rays", or UHECRs) do come from directions we can identify. We'll get to that shortly.

But first we need to talk about what sort of energies are actually involved. The most energetic UHECR ever observed had an energy of about 3×1020 eV (electron-volts). That is roughly the kinetic energy in a baseball moving at 96 km/hr. (I don't know about you, but I can't easily relate to energies expressed in terms of moving baseballs, tennis balls, or large hailstones. To me it's more meaningful to talk in terms of the energies that can be produced in the largest contemporary particle accelerators, about 1013 eV, or 10 TeV. That's more than 7 orders of magnitude, a factor of 10 million, less than the energy of some UHECRs.)

We cannot easily imagine mechanisms in "ordinary" objects (no more exotic than, say, a supernova remnant) that could on a sustained basis churn out charged particles with energies more than about 1018 eV. Up to that energy level we can envision mechanisms involving shock-wave acceleration in supernova shells. Beyond that, we would need something like some sort of quasar or active galactic nucleus (AGN). The good news is that there are very recent results relevant to both cases – cosmic rays with energies ≤ 1018 eV, as well as UHECRs.

Let's consider the lower energy case first. Here we are concerned primarily with cosmic rays originating in our own galaxy, so-called galactic cosmic rays. Many of these, of course, come from the sun, or other stars, or other equally common objects. So the ones of real interest are those having energies that call for much less common origins, yet short of things we don't have in our galaxy, such as AGNs.

The question here is whether there actually exist supernova remnants (for example) in which we can actually observe something going on that has enough energy to account for the most energetic galactic cosmic rays.

And the answer, now, is yes, we have observed such things. Just about a year ago it was reported that the Chandra X-ray Observatory had determined that the Cassiopeia A supernova remnant was accelerating electrons enough to account for all but the most energetic galactic cosmic rays. (We offered a Hubble optical image of Cassiopeia A here, and a a false color infrared image produced by the Spitzer Space Telescope here. There's an even more dramatic Spitzer image available here, and a false color image from Chandra itself here.) Here's the relevant press release:

Chandra Discovers Relativistic Pinball Machine
For the first time, astronomers have mapped the rate of acceleration of cosmic ray electrons in a supernova remnant. The new map shows that the electrons are being accelerated at close to the theoretically maximum rate. This discovery provides compelling evidence that supernova remnants are key sites for energizing charged particles.

We had a post about this here, which lists several other accounts of the discovery. (There's also news in that post about a possible extragalactic cosmic ray source.) Note that this does not say cosmic rays have actually been observed to come from Cassiopeia A – galactic magnetic fields make it unlikely to be able to prove cosmic rays come from very close to that direction. All we can say is that Cassiopeia A should be producing high-energy cosmic rays.

However, Cassiopeia A doesn't seem to be a source of the highest energy (galactic) cosmic rays we can envision coming from a supernova remnant. Fortunately, a much more recent result does provide such an example.

NASA: Major Step Toward Knowing Origin of Cosmic Rays
Since the 1960s scientists have pointed to supernova remnants -- the tattered, gaseous remains of supernovae -- as the breeding ground of most cosmic rays. These remnants expand into the surrounding interstellar gas, an energetic interaction that produces a shock front containing magnetic fields that can accelerate charged particles to enormous energies, producing cosmic rays.

According to theory, charged subatomic particles bounce like pinballs around the shock front. They pick up speed until they move nearly the speed of light. Last year, observations from NASA’s Chandra X-ray Observatory suggested that electrons are being accelerated rapidly (as fast as theory allows) to high energies in the supernova remnant Cassiopeia A.

Now, Yasunobu Uchiyama of the Japan Aerospace Exploration Agency (JAXA), and four colleagues, have observed the signature of the shock acceleration of electrons, and demonstrated that magnetic fields in supernova remnants are stronger than previously thought, and are thus fully capable of producing cosmic rays.

In a study published in the October 4, 2007, issue of the journal Nature, Uchiyama’s team used Chandra and JAXA’s Suzaku X-ray satellite to look at the northwest edge of supernova remnant RXJ1713.7-3946, located a few thousand light-years from Earth in the constellation Scorpius.

Up until this result, the problem has been a doubt that magnetic fields in supernova remnants are strong enough to accelerate particles to an energy of around 1018 eV. This doubt has been laid to rest by the observations of RXJ1713.7-3946. There it has been possible to estimate the strength of its magnetic fields.

The estimation is accomplished by Chandra observations of X-ray hot spots in the remnant. The hot spots represent synchrotron radiation given off by electrons accelerated to the highest velocities. Shock waves in the magnetic field produce the acceleration, and their velocity can be estimated at about 10 million km/hr. Such waves should give electrons a kinetic energy on the order of 1015 eV.

That's still not enough energy to account for the most energetic galactic cosmic rays, but protons (or heavier particles) accelerated to similar velocities could do the trick. Protons have the same charge as an electron (but of opposite sign). Since a proton has about 1836 times the mass of an electron, the kinetic energy of accelerated protons could reach 1018 eV, corresponding to the most energetic galactic cosmic rays. (A helium nucleus, with about 4 times the mass of a proton, could have even higher energy, of course.)

Synchrotron radiation from protons of this energy would be in the gamma-ray range, so they could not be observed by Chandra. However, there are suggestions that gamma-ray observations do confirm that the magnetic fields of RX J1713.7-3946 are strong enough to produce 1018 eV protons.

Again, as with Cassiopeia A, all this isn't saying we've observed 1018 eV cosmic rays produced by RX J1713.7-3946, only that it has magnetic fields strong enough to do the job.

Other reports of this research: here, here.

We're still left with the problem of explaining UHECRs. Since we can't imagine anything inside our own galaxy that could be energetic enough to produce UHECRs without being directly observable (and certainly we don't observe any such thing), the source must be outside the galaxy.

As the following recent note observes, there are a few possibilities.

Magnetic cocoons power energetic cosmic rays
[U]ltra-high-energy cosmic rays (UHECRs) – each packing the punch of a baseball – are an outstanding mystery. Although it is conceivable that they are produced near the Milky Way by the decay of super-heavy dark matter particles or by defects in space-time, the most likely sources are the most powerful objects in the universe – 'active' galaxies whose colossal black holes are devouring nearby matter, and gamma-ray bursts. These are far beyond our galaxy – and herein lies a very serious problem.

The problem is what is called the Greisen-Zatsepin-Kuzmin (GZK) limit. This limit results from the fact that protons (or heavier atomic nuclei) that have an energy more than about 6×1019 eV will interact with photons of the cosmic microwave background (CMB). The interaction destroys the cosmic ray particle and produces short-lived pions, which decay long before reaching Earth. For a UHECR the probability of an interaction is proportional to the distance between the Earth and the cosmic ray source.

The reason this occurs is that cosmic rays with this energy are moving at very close to the speed of light. From the point of view of the cosmic ray itself, a microwave photon is drastically blue-shifted, even though to an observer on Earth, a CMB photon has quite low energy. But for a cosmic ray moving fast enough, the CMB photon appears to be very energetic, and the threshold above which a pion-producing interaction can occur is for cosmic rays with energies above 4×1019 eV.

This diagram show the expected flux of cosmic rays as a function of their energy, assuming a power-law distribution. This is in fact what is observed. For example, cosmic rays with an energy of more than 1019 eV are observed at a rate of only 1 per km2 (of Earth surface) per year. So you need to observe over an area of many km2 simply to tally a reasonable number of the most energetic cosmic rays in a few years.

Because of the GZK effect, the flux of cosmic rays takes a sharp drop below the curve in the diagram right around 4×1019 eV. We still observe a very few cosmic rays with energies above that point, because if the cosmic ray originates from a source sufficiently close to Earth, there is still some nonzero probability it will not collide with a CMB photon. However, there is essentially no chance we will see a cosmic ray of more than 4×1019 eV if its souce is more than about 250 million light-years (Mly) from Earth.

As it turns out, this limit is actually a stroke of good fortune, because it means that in order to identify sources of UHECRs we need only consider objects within an Earth-centered sphere of radius 250 Mly. We can simply disregard objects that are farther away.

Another simplifying condition is that we don't need to bother with cosmic rays having an energy less than about 3×1019 eV, because the trajectories of such lower-energy cosmic rays are likely to have been deflected by our galaxy's magnetic field. We couldn't hope to identify the direction from which they came anyway. This is a useful simplification, since there is a larger variety of possible sources for the lower energy cosmic rays, and we would simply have too many possibilities to have a hope of correlating the observed directions with locations of particular source types. Furthermore, atomic nuclei larger than one proton will have more than one unit of charge, so they will also be deflected by the galaxy's magnetic field. And so we would not expect cosmic rays that don't consist of individual protons to have a correlation with the location of specific source objects.

Given all that, it's easy to understand and appreciate the result that was just announced early in November. The result comes from a large team working at the Pierre Auger Observatory in Argentina. The result, in a nutshell, is that out of 15 cosmic ray events with energy more than 6×1019 eV counted since 2004, 12 came from a direction that was within 3.1° of a known active galactic nucleus (AGN) within 250 Mly of Earth. It is calculated that the probability of this correlation occurring by chance is only about 1 in 1000 if the flux were isotropic.

What about the other 3 (of 15) events? They might have been cosmic rays that consisted of atomic nuclei heavier than a proton, and hence were deflected by galactic magnetic fields. However, these anomalous events were observed near the galactic plane, so their source could have been an AGN we cannot see because of dust in the galactic plane.

It should be mentioned that Auger is nothing like a typical optical observatory. Instead, it consists of a large number of instruments spread over an area of 3000 km2, which is about the size of Rhode Island. Yet since observations began in 2004, only about 80 events with energy more than 4×1019 eV were tallied, and there were only 27 with energy more than 5.7×1019 eV (a rate of about 1 per 4 km2 per century), so you can see how rapidly the numbers drop off in this range. Small wonder that cosmic ray astronomers now want to have an even larger observatory built, as well as to continue observations over enough years to reduce the possibility that correlations are due to chance.

Even so, the present results are generally considered to be pretty important – enough, anyway, to have become the cover story of the November 9 issue of Science. And this is even though the result is "only" a statistical correlation between directions of events and known AGNs. It's much too soon to say something like N events have been observed very close to a specific AGN. Also still left open is the construction of a model for exactly how UHECRs are produced in an AGN, let alone the validation of the model in a particular case (as has been done with lower energy cosmic rays and supernova remnants).

It's also only fair to note that objections to the Auger conclusions have been raised – see here, and in some of the references below.

However, we now have a lot better information about UHECRs than we had before.

More information:

Blog articles:

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Physical sciences news, 12/3/07-12/9/07

Active galaxies
Jets of high-energy particles are produced by a variety of astronomical objects. The largest example of this phenomenon has been discovered in the active galaxy CGCG 049-033.

Intergalactic particle beam is longest yet found
A Million Light Years

Galaxies in the early universe
The earliest stars in the universe consisted entirely of primordial hydrogen and helium, since heavier elements were formed almost entirely by the demise of these first stars in supernova events. Planets (which are generally considered a necessity for the development of life in any form similar to what we know) require elements heavier than hydrogen and helium. New simulations suggest that the earliest stars, having masses of perhaps 100 Suns, may have formed earlier than previously supposed, meaning that planets (and life) could also have formed earlier.

Earliest galaxies had building blocks of life

Dark matter stars
Many observations indicate that dark matter in the universe is about 5 times as plentiful (by mass) as "ordinary" baryonic matter. Consequently, the first compact objects to form in the universe may have consisted mostly of dark matter. Although ordinary matter would have been mixed in, the dark matter could have prevented, for a time, ordinary matter from collapsing to a density sufficient to form stars powered by thermonuclear reactions.

‘Dark stars’ may have populated early universe
Drowning in Dark Matter?
Universe's first stars may have been dark
First Stars Were Huge and Dark
Dark matter in newborn universe doused earliest stars
Dark matter and the first stars: a new phase of stellar evolution

Dark matter in galaxies
Computer simulations of the early universe, until now, have predicted larger amounts of dark matter in the central parts of galaxies than is actually observed. Refined simulations that take into account the supernova explosions of the first generation of stars now indicate that gravitational effects of the supernovae could have driven much of the original dark matter out of the central regions of galaxies.

Galaxies Are Born Of Violence Between Dark Matter and Interstellar Gas
Invisible Matter Loses Cosmic Battle

Gas giant planets
Most extrasolar planets that have been detected so far are gas giants located very close to the central star – because this is the configuration most likely to be detected by current technology. Some of these planets are so close to their star that it has been difficult to understand how they have escaped being completely evaporated by the heat. New simulations indicate that positively charged hydrogen ions containing three protons are capable of radiating away enough heat to allow gas giant planets in close proximity to their stars.

Planets can survive extreme roasting by their stars
How to Destroy a Giant Planet

Cosmic textures
Phase transitions, such as occur in the freezing of ice and other solids, should also have occurred very early around the hypothesized time of inflation in big bang models of the universe. Such transitions may have led to inhomogeneities called "topological defects", which in principle could lead to observable inhomogeneities in the cosmic microwave background. Theoretical calculations now indicate that particular types of defects called "textures" may account for puzzling features actually observed in the microwave background.

Possible Cosmic Defect, Remnant From Big Bang, Discovered
A Texture in the Sky?
A Cosmic Microwave Background Feature Consistent with a Cosmic Texture

White dwarfs in globular clusters
Astronomers have been surprised to find that white dwarf stars are unexpectedly scarce in the central regions of some globular clusters. It is hypothesized that the explanation for this may lie in asymmetrical flows of gas out of stars in their red giant phase, just before the star collapses to a white dwarf.

Sun-like stars get a kick out of death
Dead Stars Propelled Like Rockets

The solar corona
Observations that have been deduced from data collected by the Japanese Hinode mission may have solved a long-standing mystery of why the Sun's corona is so hot – several million degrees K – even though the solar surface is only about 6000° K. The cause appears to be strong magnetic turbulence in the corona, called "Alfvén waves".

Mission illuminates solar mysteries
Roiling magnetic waves explain solar enigma
Unlocking the riddle of Sun's heat
Results from Hinode: Sunrise on Coronal Heating
Are There Alfvén Waves in the Solar Atmosphere?
Magnetic waves make solar wind howl
Unlocking the riddle of Sun's heat
The Mystery Of Our Sun's Heat
Hinode reveals new insights about the origin of solar wind
Hinode: new insights on the origin of solar wind

Slushball Earth
It now appears possible that the Earth's oceans never entirely froze solid, as hypothesized in the "snowball Earth" scenario. Carbon dioxide dissolved in the oceans, coming from carbonate minerals on the ocean floor, may be responsible for a milder freeze that produced only a "slushball".

Did Carbon Save Earth From a Deep Freeze?
'Snowball Earth' was more a slushball

Interruption of the Gulf Stream
About 8200 years ago a huge (100,000 km3, seven times the volume of the present Great Lakes combined) North American glacial lake known as Lake Agassiz had swelled so large that it burst out and mostly flooded into the Atlantic Ocean. There is now evidence that all this cold, dense fresh water was sufficient to disrupt the flow of the Gulf Stream and cause a temporary but severe cooling of the climate.

Ancient flood brought Gulf Stream to a halt
Epic Flood Triggered Ancient "Big Chill," Study Says

Scientists have generated, modulated and electrically detected a pure spin current in silicon. This could be a key step in the development of silicon-based "spintronic" devices, which might be used to make denser information-processing devices than can be implemented using present technology based on currents of electric charge.

Scientists generate, modulate, and electrically detect pure spin currents in silicon

Messier 74 - NGC 628

Saturday, December 8, 2007

NASA/ESA Hubble Space Telescope image of the nearby spiral galaxy Messier 74 (11/29/07)
In the new Hubble image we can also see a smattering of bright pink regions decorating the spiral arms. These are huge, relatively short-lived, clouds of hydrogen gas which glow due to the strong radiation from hot, young stars embedded within them; glowing pink regions of ionized hydrogen (hydrogen that has lost its electrons). These regions of star formation show an excess of light at ultraviolet wavelengths and astronomers call them HII regions.

Tracing along the spiral arms are winding dust lanes that begin very near the galaxy’s nucleus and follow along the length of the spiral arms. These spiral arms are not actually static ‘arms’ like spokes on a wheel. They are in fact density waves and move around the galaxy’s disc compressing gas – just as sound waves compress the air on Earth – creating a new generation of young blue stars.

Messier 74 (NGC 628) – click for 1280×1024 image

Physical sciences news, 11/26/07-12/2/07

Monday, December 3, 2007

Climate change
To the surprise of practically nobody except climate change denialists, levels of CO2 in the atmosphere continued to increase in 2006 to new record levels. And Scientific American comes up with a nice suite of several articles (two listed here), which key off the recent report of the U.N. Intergovernmental Panel on Climate Change.

U.N.: Greenhouse Gases Hit High in 2006
Beyond the Worst Case Climate Change Scenario
10 Solutions for Climate Change

Some results are in from the European Space Agency's Venus Express mission, and they paint a picture of Venus as not such a great place for your next summer vacation. Much of the crappy climate is due to a CO2-induced greenhouse effect. Uh, oh.

How Earth's twin became so hellishly hot
NASA Scientist Confirms Light Show on Venus
Venus: Earth’s twin planet?
Probe likens young Venus to Earth
Twin Planets Earth and Venus Were "Separated at Birth"
Signs of Lightning on Venus
Venus offers Earth climate clues
Did life once thrive on Evil Twin Venus?
Venus: The Un-Twin of Earth
Venus May Be Earth's Hellish Twin
Lightning detected on "evil twin" Venus
'Evil twin' Venus astounds astronomers
Venus inferno driven by greenhouse effect
Researchers publish two articles in Nature on latest discoveries on Venus

The Milky Way and its neighborhood
Two things here about our galactic neighborhood. We might have another neighbor galaxy that has never actually been seen yet, even though it's almost as close and as large as the Andromeda galaxy. And there's a cluster of very young stars – only 100 light-years from our galactic center – that's moving way too fast.

Milky Way galaxy may have hidden twin
Dynamical Constraints on the Local Group from the CMB and 2MRS Dipoles
Star cluster's extreme speed puzzles astronomers
The proper motion of the Arches cluster with Keck Laser-Guide Star Adaptive Optics

Early galaxies
Astronomers using Europe's new Very Large Telescope, located in Chile, have observed 27 young "proto-galaxies" as they appeared about 2.5 billion years after the big bang. This provides evidence that larger galaxies like our own may have formed by the amalgamation of a number of such proto-galaxies.

Faint galaxies spotted in the early universe
Proto-galaxies tip cold dark matter
A Long, Hard Look at the Early Universe
Discovering Teenage Galaxies
Sighting of 'teenage' galaxies gives scientists
stellar return

New population of faint protogalaxies discovered
A Population of Faint Extended Line Emitters and the Host Galaxies of Optically Thick QSO Absorption Systems

Formation of planetary systems
Astronomers think they have found the two youngest solar systems ever detected, about 450 light-years from Earth. Elsewhere, one bright, massive young star in the Trapezium of the Orion Nebula is pumping out hot gas at a temperature of about 2 million degrees C, and this probably affects the formation of planetary systems around other nearby young stars.

Astronomers Discover Youngest Solar Systems Ever
Planet Formation is Child's Play
Of Young Stars and Ancient Planets
Million-degree galactic gas 'bubbles' found
Huge Stars Seen as Source of Glowing Gas
Million-Degree Plasma Pervading the Extended Orion Nebula
An X-Ray Santa Claus in Orion

Preon nuggets
Preons are hypothetical particles that have been proposed to make up quarks. Although there is as yet no experimental evidence for preons, if they ever existed in the universe soon after the big bang, a few preon clumps might still survive as objects a few centimeters in size but with as much mass as the Moon.

Nuggets of New Physics
The observational legacy of preon stars - probing new physics beyond the LHC

Large clumps of hydrogen and helium in the early universe may have condensed into star-like objects initially 1000 times as massive as the Sun. Although the core would collapse into a black hole, the resulting "quasistar" might be massive enough to avoid destruction, and continue to accrete matter, evolving into a supermassive black hole such as seems to exist in the center of most galaxies.

Biggest black holes may grow inside 'quasistars'
Quasistars: Accreting black holes inside massive envelopes

Philosophia Naturalis #15 has been published

Saturday, December 1, 2007

Sam Wise at Sorting Out Science has put together a great collection of posts. It's a wonderful look at a number of different viewpoints on a lot of recent news in the physical sciences. Thanks, Sam.

You can find links to all previous editions of the carnival, and information on how to submit a blog article or volunteer to host the carnival, at the Philosophia Naturalis home page.

A Galaxy for Science and Research

Saturday, November 24, 2007

A Galaxy for Science and Research
NGC 134 is a barred spiral with its spiral arms loosely wrapped around a bright, bar-shaped central region. The red features lounging along its spiral arms are glowing clouds of hot gas in which stars are forming, so-called HII regions. The galaxy also shows prominent dark lanes of dust across the disc, obscuring part of the galaxy's starlight.

NGC 134 – Click for 1280×1024 image

More: here

Japanese robot not quite ready for prime time

Thursday, November 22, 2007

No further comment...

New Hitachi Robot Rolls Around, Crashes
Hitachi's new toddler-like robot rolled around and waved for reporters Wednesday, only to crash into a desk and demonstrate the challenge of turning automatons into everyday helpers.

The red and white robot, designed to run errands in offices, wasn't prepared for the jam of lunch-break wireless network traffic at the company's research center. Unable to communicate with its handler's laptop, it smashed into the office furniture as reporters gasped.

The discovery of sirtuins, part 2

Tuesday, November 20, 2007

Unless you're a biologist who's already familiar with the ins and outs of research into sirtuin proteins, you might want to have a look (if you haven't already) at the previous note in this series, where I describe a lot of important background and provide various other references.

But if you're ready to forge ahead, in this note I'm going to write about a gene found in the nematode Caenorhabditis elegans. The gene is called sir2-1, and it's a homologue of the yeast SIR2 gene. (I. e. the two genes have very similar DNA sequences.)

C. elegans and some of its genes (like sir2-1 and several others affected by it, as mentioned here and here) has been studied by many investigators, because it's an easily-grown model organism for many biological processes that occur in multicellular creatures. And that's in spite of its simplicity – adults have a grand total of only 959 somatic cells.

Sydney Brenner began research into the detailed biology of C. elegans in 1974. Brenner had already earned his scientific spurs for helping decipher the 3-letter DNA code in the 1960s. But the Nobel Prize he shared in 2002 was awarded for his work with worms – which is an impressive statement about the importance of that work. Other prominent names associated with research into C. elegans include Cynthia Kenyon and Gary Ruvkun.

However, for the initial study of SIR2-like genes in C. elegans, we can return to the laboratory of Leonard Guarente. Soon after he and others at the lab had begun to appreciate the importance of SIR2 for longevity in yeast, Guarente suggested to a postdoc in his lab, Heidi Tissenbaum, that it might be very rewarding to figure out whether there were similar genes in the nematode that played a role in longevity. Tissenbaum was a pretty natural choice for this project, since she'd just recently done her thesis work in Gary Ruvkun's lab.

Despite the simplicity of C. elegans, following up on this suggestion was more easily said than done. Some idea of the complexity involved can be gained from the fact that there are about 20,000 genes in the worm's genome, as had only very recently been realized, since C. elegans was the first animal to have its whole genome figured out. The worm has almost 90% as many different genes as a human.

Among these 20,000 or so genes were four that were like SIR2. Which, if any, of those might have longevity-prolonging effects? Guarente and Tissenbaum set about trying to answer the question. So as not to miss any genes that might affect longevity even though unlike SIR2, they did experiments that could turn up others among the 20,000. They did this by considering different strains of C. elegans, each of which had one random section of its DNA duplicated. Since a eukaryotic organism already has two copies of each gene, this meant each strain would have 50% more copies (3 instead of 2) of the genes on the duplicated segment.

They found only one out of the 40 strains they tested that had a significantly longer life span. And the duplicated section of DNA contained only one of the 4 known SIR2-like genes – sir2-1, which was also the one closest in sequence to SIR2. Talk about "things that make you go hmmmmmm..."

To further strengthen the evidence that sir2-1 was somehow responsible for the increased life span, Tissenbaum produced a strain of C. elegans whose only extra gene was one or more extra copies of sir2-1. Lo and behold, these worms indeed lived much longer.

That's all well and good, of course. But how does sir2-1 bring about this increased life span? It certainly couldn't be much like the way SIR2 works in yeast to raise longevity. As you recall, longevity in a yeast cell is measured by how many times it is capable of budding off daughter cells. Normally, this is about 20 times. But this number can be substantially increased in a yeast strain with extra copies of SIR2.

However, the biology of C. elegans is quite different. The life span of these worms is manifested in a very different way than by how often cells are capable of dividing. In fact, the cells of an adult nematode do not divide at all – they have reached a state known as "senescence", all 959 of the somatic cells. All the difference in life span of a nematode occurs after its cells become senescent.

Initially, life span of the worms was measured simply by how long it took before the creature stopped wriggling, about 20 days. Later, more careful observation showed that aging could actually be noticed visibly (under a microscope). Old worms looked wrinkled and exhibited other visible signs of decrepitude. This is of importance, because an alternative hypothesis about how sir2-1 promoted longevity was that it somehow blocked a disease state that could kill the worm. But in fact, it was found that extra sir2-1 genes indeed slowed the rate of visible aging.

So there still remained to find an account of how sir2-1 extended life span. There were several other worm genes that were already known to affect longevity. I noted two of these (daf-2 and daf-16) here. Some of this information was already known to Guarente and Tissenbaum. In fact, the latter herself had participated in some of the relevant research while working in Ruvkun's lab. This 1997 press release describes some of that research:

Inactivation Of Key Gene Allows Worms To Develop Without Insulin (10/29/97)
The team — which also includes first author Scott Ogg, PhD, Suzanne Paradis, Shoshanna Gottlieb, PhD, Garth Patterson, PhD, Linda Lee, and Heidi Tissen baum, PhD — discovered that insulin may control metabolism via inactivation of a second gene, daf-16. The researchers found that, although insulin normally is required to regulate metabolism in the worm C. elegans, as in humans, the animal no longer needs insulin if it also carries a mutation in daf-16. This gene encodes a DNA-binding protein that passes along insulin signals within the cell to control the production of enzymes that metabolize sugars and fats. The team proposes that in the absence of insulin, the DAF-16 protein becomes unregulated, and that its runaway activity may be the key cause of metabolic disease in diabetes. In support of this model, the research team shows that metabolic defects in worms with defective insulin signaling are "cured" by the inactivation of the daf-16 gene.

(If you're confused by the capitalization of daf-16 and DAF-16, note that the former refers to the gene, and the latter to the corresponding protein. But you're not alone, since the opposite convention is sometimes used.)

I suppose that, at this point, the suspense is killing you, or at least delivering a credible threat to curtail your life span, so I'll just summarize what has been learned over the years about daf-2, daf-16, related genes, and how sir2-1 fits into the picture.

The hormone insulin plays an important role. In mammals insulin has a signaling function that stimulates cells to take up glucose and metabolize it. However, its role in C. elegans is somewhat simpler. There it doesn't directly affect glucose metabolism, but it still acts as a signal, as a trigger of the so-called "insulin-signaling pathway". This pathway keeps the daf-16 gene turned off as long as a cell-surface receptor detects insulin.

The protein coded for by daf-16, namely DAF-16 (duh), is a transcription factor, which means it enables the expression of other genes. When this happens in an immature worm, the result is an alternative developmental path, in which the worm enters a larval state, called a "dauer" (German for "enduring"). (The name "daf" is short for "dauer formation".) A dauer will eventually, after some delay, develop into a normal adult anyhow. But evolution has provided this dauer stage in case times are lean, and a delay will allow the organism to survive a little longer, on the hope that better times will come soon.

Under normal conditions, when sufficient nutrients are available, insulin is produced. A cell surface receptor (DAF-2, coded for by daf-2) detects the insulin and initiates a signaling cascade within the cell, and this in turn keeps daf-16 inactive. This does no harm to the organism, and in fact worms get along just fine even without a daf-16 gene, assuming adequate nutrition.

However, assuming insufficient nutrients, insulin levels drop. If that happens early enough in the nematode's life, daf-16 becomes active and triggers the dauer state. But what occurs after the nematode reaches adulthood and daf-16 becomes active (due to low insulin level) is perhaps even more interesting: the worm's aging slows down, and total life span increases. So this is a second way that the worm, even after it reaches adulthood, may be able to survive when food runs low, in the hope for better times.

Why isn't this second scenario simply the normal one? Why bother with the dauer stage at all? The answer is probably that nature has found this "live fast and die young" strategy the most successful in the long run, just as with small rodents. After all, a C. elegans is pretty small – 959 cells and about 1 mm in length. It's easy prey to larger predators that can enjoy a nematode meal. On the other hand, in cases there's not enough food for the worm to "live fast", it's nice to have not one but two backup strategies.

So where does sir2-1 fit in to all of this? Well, just as with SIR2, the worm homologue produces a deacetylase enzyme that inhibits the production of other proteins. One or more of these proteins is a necessary part of the signaling cascade that insulin initiates to keep daf-16 inactive. So extra sir2-1 protein interferes with the insulin signaling and, in effect, activates daf-16, which slows down aging, and extends life span – even when adequate amounts of nutrients are available.

Pretty neat, eh? That's evolution for you – always coming up with the Rube Goldberg schemes.

OK, that's how sirtuins work in nematodes. What about mammals, like us? As you might suppose, since mammals have far more than 959 cells in their bodies, things are a lot more complicated. There are even (at least) seven different homologues of SIR2. But the fact that in worms sir2-1 messes with insulin signaling and metabolism is a clue. Those are pretty important processes in mammals too.

To be continued.


Further reading:

daf-16: An HNF-3/forkhead Family Member That Can Function to Double the Life-Span of Caenorhabditis elegans (11/14/97)

Reproductive Signals Affect Lifespan In Roundworm C. Elegans, Offering Possible Insight Into Human Aging Process (5/27/99)

Smell, Taste May Influence Lifespan Of The Roundworm C. Elegans (12/17/99)

Long-Lived Worms (3/8/01)

University Of Colorado Researchers Identify Switch That Controls Aging In Worms (12/11/01)

Stem Cells For Eggs And Sperm Also Control Aging In Roundworm (1/18/02)

DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism (4/25/03)

Scientists Find What Type Of Genes Affect Longevity (7/1/03)

Old Worms, New Aging Genes (8/2/03)

Methuselah Worm Remains Energetic for Life (10/27/03)

Signs Of Aging: Scientists Evaluate Genes Associated With Longevity (4/18/05)

For The First Time: Longevity Modulated Without Disrupting Life-sustaining Function (3/11/06)

Eat Less, Live Longer? Gene Links Calorie Restriction To Longevity (5/2/07)

Genes That Both Extend Life And Protect Against Cancer Identified (10/15/07)


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