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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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The discovery of sirtuins, part 1

Saturday, November 17, 2007

There's a lot more to the story of sirtuin proteins beyond what I've barely touched on here and here. Perhaps the best way to proceed is to rewind the tape (now, there's a metaphor on it's way out if there ever was one) to the point where biologists initially recognized what the story was about and where it might be going.

The best reference for this is Leonard Guarente's 2003 book Ageless Quest. Since Guarente seems to have played the largest role in the initial understanding of sirtuins, this reference is pretty much definitive. This book is short and readable, but packed with information. It seems to be rather underappreciated. However, if you don't happen to have it at hand, a few more brief references are listed at the end of this note.

Guarente isn't especially explicit about the dates of various milestones, so one has to infer a bit, but his memoir begins roughly in 1987, with the most important results it discusses coming out around 2000. The story begins after Guarente has received tenure in MIT's biology department and has begun to assume responsibility for a laboratory of his own. Until 1991 the lab's primary focus was gene transcription, but then (as now, and for good reason) that was a crowded field.

Gradually Guarente decided that investigation of the process of biological aging, and in particular the study of genes that regulate aging, was both less crowded and more interesting. Of course, the field was uncrowded for a reason – most biologists at the time considered the problem of aging to be too hard, and out of reach of serious scientific research. Guarente, however, succumbed to the challenge.

In 1991 he decided that yeast (genus Saccharomyces), a single-celled eukaryote, was the right model organism to begin with. It was simple enough to make research practical, but complex enough to exhibit the characteristic phenomena of aging seen in much more complicated multicellular organisms. Yeast cells reproduce by budding off copies of themselves. This process typically repeats through 20 to 40 iterations before any given cell becomes unable to reproduce, and eventually dies. (This is different from what happens with bacteria, which are prokaryotes and are able to continue dividing indefinitely.)

A newly-budded yeast cell is at a peak of generative vigor. This is regardless of the age of its mother cell – an important clue, as we'll see later. The new yeast cell may start budding daughter cells once an hour, but gradually slows down. At between 1 to 4 hours per iteration, 20 iterations typically occur in 40 to 60 hours. However, an intriguing fact is that different yeast strains are capable of continuing to reproduce for a variable number of iterations, up to a maximum of about 40. So the scientific problem is to figure out what accounts for the difference. Presumably, it's some small difference in the genes found in different strains of yeast. But what genes?

To keep the narrative brief, I'll leave out most of the details. Suffice it to say that the first clues came when a lab worker came across one batch of yeast with exceptional longevity. So what was different about its genes? Suspicion quickly focused on variants of a particular gene, which had already been named SIR4. SIR is an acronym for Silent Information Regulator, and SIR4 was already known to be a regulatory gene that silences the expression of other genes.

In yeast, SIR4 is frequently found in association with other SIR genes – SIR2 and SIR3, although these don't have similar amino acid sequences. So the question became, what other genes does SIR4 (and its associates) regulate, when, and why?

Initially suspicion focused on the possibility that the longevity effect of SIR4 was related to chromosome teleomeres. These structures, which occur at the ends of chromosomes, were already known to have an effect on the ability of a eukaryotic cell to divide. This clue turned out to be a red herring, as was eventually realized. But before enlightenment fully dawned, Guarente and some of his collaborators in the lab published a paper in the prestigious journal Cell, in 1995, reporting that the gene triple of SIR2, SIR3, and SIR4 affected some as-yet not well determined part of the yeast genome in such a way as to extend longevity under some circumstances.

The important question, then, was to determine exactly how this came about. Other labs besides Guarente's were also studying yeast and the SIR genes, and they made significant contributions. But to keep this simple, I'll continue to focus on the Guarente lab. The next advance, after the 1995 paper, involved certain curious DNA structures called "rDNA circles".

A new postdoc named David Sinclair, who Guarente recruited to join the lab in 1995, had some of the crucial insights, which involved rDNA. That is the name given to a certain part of the yeast genome that codes for RNA sequences used in building the cell structures known as ribosomes.

In the overall process of replicating chromosomes during cell division, a subprocess called recombination occurs. Normally, a strand of DNA in one chromosome of a pair is broken at a certain place, and "recombined" with a strand of DNA from the other member of a pair of chromosomes. The way that the process "ought" to work is that the DNA is broken and recombined at exactly the same place in the two strands, as determined by the sequence of genes within the DNA. However, rDNA happens to contain multiple copies of the same gene, in order to produce enough corresponding RNA needed to make ribosomes. So it's possible for mistakes to be made in which some copies of the ribosomal DNA genes are deleted from the resulting recombined DNA strands. The leftover rDNA genes float away in little rings of DNA called rDNA circles.

This circumstance is somewhat unique to yeast, due to the way the rDNA genes are laid out in yeast genome. So if all this was part of an aging mechanism, it wouldn't necessarily be applicable except in yeast. What is really surprising is that relevant mechanisms for other species were eventually found, but that's getting ahead of the story.

One result of the production of rDNA circles in yeast is that after awhile fewer genes remain in the chromosomal DNA to produce ribosomes for the cell's needs. Perhaps eventually there doesn't remain an adequate number of these genes, and this fact is responsible for yeast aging. But there's another possibility. Perhaps an increasing number of these rDNA circles accumulate in yeast cells, and eventually this is what gums up the cellular works and causes aging.

It was Sinclair who came up with this idea, and one clue which led to it is, as mentioned before, that newly budded daughter yeast cells have the maximum life expectancy that normally occurs with yeast cells of their lineage. They did not seem to inherit any premature aging from a mother cell that could already have budded many times before. This would indeed be a problem if too many rDNA genes became lost in the process of repeated recombination, to be sloughed off into rDNA circles. Instead, Sinclair suspected that what was happening was that the rDNA circles were themselves being cloned repeatedly by the process of recombination. And further, that all such cloned rDNA circles remained in the mother cell, instead of any being passed along to daughter cells. He managed to show, in a series of experiments, that this latter scenario was what was actually happening, and did cause aging in yeast.

In late December of 1997 Guarente and Sinclair published a paper in Cell, described at length in this press release, which reported these results. The paper attracted a considerable amount of attention, including a long front-page article in the New York Times, by science writer Nicholas Wade. (I mention Wade specifically, because he has remained interested in the topic, and wrote a perceptive article for the Times in November 2006 on resveratrol, which I discussed here.)

In spite of all this progress, one important part of the puzzle remained to be solved. That is, what exactly is the role, if any, that the SIR genes play in the whole process? It was already clear that they did affect the longevity and rate of aging of yeast cells, but how?

It turned out that it wasn't actually SIR4 that affected yeast cell longevity, as initially suspected, but instead its associate SIR2. And the mechanism for this that was discovered has profound implications for aging in many eukaryotic species, not just yeast.

The importance of SIR2 instead of the other SIR genes in yeast was recognized when it was found that permanently deactivating SIR2 drastically reduced yeast lifespan, but deactivating SIR3 and SIR4 had little effect on lifespan. So investigation quickly focused on SIR2. What was it doing? Sinclair moved on to become a professor at the Harvard medical school in 1999 and continued to study the problem. But Guarente and others in his lab, as well as many others outside the lab, also pressed on.

So SIR2 was the critical gene, but why? SIR2 was already known as a silencing gene, meaning it inhibits the expression of other genes. It turned out that in yeast, one thing SIR2 does is to suppress the process of recombination that produces all those rDNA circles. And how does it do that? (A new question seems to arise every time another one is answered.)

SIR2 does its work, at least in this case, because its enzymatic action (or rather, the action of the protein – Sir2 – encoded by SIR2) is to remove acetyl groups from other proteins. That's why Sir2 is called a deacetylase enzyme. The presence, or absense, of acetyl groups on a protein can determine whether or not the protein performs a specific function. So acetylation can by itself alter the expression of the gene that encodes the affected protein.

However, Sir2 doesn't act on just any old proteins, but specifically on histone proteins. You recall, of course, that a histone is a type of protein that comes together in groups of eight to make up a nucleosome. A nucleosome, in turn, is like a spool around which 146 base pairs of a DNA strand are wound, as one of many beads on a string that make up the chromatin constituting a chromosome. So Sir2 is actually a histone deacetylase enzyme (HDAC), such as described here. And when a histone is deacetylated, it becomes impossible for the gene whose base pairs are affected to be expressed, quite effectively silencing the gene.

And that's still not all. It turns out that Sir2 can perform this deacetylation only with the help of a relatively small molecule, called nicotinamide adenine dinucleotide, or NAD for short. (Such a helper molecule is called a coenzme.) NAD turns out to be critically important here, because it is centrally involved in cell metabolism.

When a cell is starved for nutrients, the levels of NAD will be high, enabling Sir2 to perform the deacetylase function. And as it happens, in yeast the genes that are consequently silenced are the very ones that cause the production of the rDNA circles. Putting this all together, a yeast cell that is starved for nutrients will cut back the process that plays a key role in cellular aging.

It's very clever of evolution to have come up with this Rube Goldberg mechanism. The net result is that yeast cells that are ill-nourished automatically cut back their rate of aging, so that they may survive until adequate nutrients may become available. Of course, evolution wouldn't have needed to be so clever if it hadn't also allowed aging to occur in the first place, because of (in this case) the production of inconveniently many rDNA circles. This all illustrates the unplanned, rather haphazard result of evolutionary processes.

Guarente and some of his lab associates published a paper describing all this in a February 2000 technical paper in Nature. That paper is announced here. A couple of months later, he composed a review, described here. That description began by noting
Caloric restriction, which is the reduction of caloric intake without malnutrition, is a time proven method for extending the life span of mammals and postponing the manifestations of aging, including both functional decline and age-related diseases. Much is know about the physiological changes that occur in animals subjected to caloric restriction, but molecular mechanisms involved in this phenomenon are poorly understood because of the lack of workable experimental models.

That press release continued to say
Dr. Leonard Guarente of the Massachusetts Institute of Technology announced that his lab has identified a gene, SIR2, which regulates the life span of yeast. The gene is responsible for the production of a protein, Sir2, and the higher the level of this protein, the longer the life span of yeast cells. Sir2 is responsible for a process called genomic silencing that Dr. Guarente believes helps slow the aging process. However, it requires help of another compound, the level of which is determined by metabolic rate, to do this.

"Our findings thus provide a model for aging that is universal and explains how calorie restriction extends life span," says Dr. Guarente. "We believe that these studies could lead to the development of a drug that intervenes to strengthen the Sir2-silencing process and provides the benefits of calorie restriction without the extreme difficulty of the regimen itself."

Of course, all he was claiming here is a possible model for the longevity-enhancing effects of calorie restriction. At best the model had experimental support in the case of yeast. What about more complex organisms, such as, for example, the nematode Caenorhabditis elegans?

C. elegans was next on the agenda, and surprisingly enough (or maybe not), a nematode gene very like SIR2 was also implicated in extending lifespan, though through a rather different mechanism. However, we'll have to tell that story later.

To be continued.


Further reading:

Unlocking the Secrets of Longevity Genes – Article by Guarente and Sinclair published in Scientific American in 2006, discussing the state of knowledge at the time of the relationships between sirtuins, calorie restriction, and aging.

SIR2 and aging: an historical perspective – A very brief sketch of the subject.

Gaurente Lab – A brief overview of relevant discoveries made at the lab.

Guarente research summary – Very brief summary of Guarente's own research and short list of publications.

Genes Linking Aging and Cancer – A recent blog post that discusses recent findings about the role of sitruins in both aging and cancer.

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Sirtuin proteins

Friday, November 16, 2007

What's a sirtuin protein? Perhaps this will jog your memory. Not quite two months ago I wrote about resveratrol – the trace ingredient in red wine that may (or may not) have longevity-extending effects. See the article for plenty of details, but there are a few summary points to repeat here.

First, resveratrol may not occur in sufficiently high concentrations in red wine to offer practical health benefits to humans. Second, there are other compounds in red wine (and red or purple grape skins) which may play a larger role than resveratrol in the reported health benefits of red wine. Third, it is suspected that some of the health benefits observed in experiments with mice fed diets having high concentrations of resveratrol may be a result of its activation of a gene that produces the enzyme called SIRT1, which is a "sirtuin" protein. But, fourth, the observed health benefits of resveratrol may also be due to other effects. In summary, that situation with red wine and resveratrol is still not very clear.

However, it's specifically the sirtuin protein SIRT1 (and some closely related variants) we're interested in here, for reasons we'll get to in a moment. But to set the stage a little further, SIRT1 itself (and related proteins) has been of interest to biologists for over ten years because SIRT1 and its relatives appear to affect the longevity (usually in a positive way) of individuals belonging to several diverse eukaryotic species, ranging from yeast and nematodes to mammals. And this effect seems to be closely related to the observed beneficial effects on longevity of calorie restriction – effects that have been observed for many decades.

There's a little history behind the name of the protein SIRT1. It begins with certain proteins, which were observed in yeast, and which seemed to have something to do with the longevity of yeast cells. There were several of these proteins, which were called Silent Information Regulators. Three of them, in particular, known as SIR2, SIR3, and SIR4, seemed to be implicated in the longevity effect, although they are not structurally similar. Ultimately SIR2 proved to be the most important, and remarkably, a gene in the nematode Caenorhabditis elegans turned out not only to be a close analogue of SIR2 but also to have similar longevity-enhancing effects.

Because of their interesting effects, such proteins became known as "sirtuins" (get it?). It turns out that there are at least seven similar human proteins, named SIRT1 through SIRT7. Of these, it is SIRT1 that has (for good reason) attracted the most attention. It is an enzyme, in particular a histone deacetylase enzyme. Such enzymes are able to efficiently silence the expression of a variety of genes, so they are involved in a wide diversity of biological processes, as I've written about before. (And as I hope to write much more about.)

There are all sorts of interesting things to note about the human sirtuins, but the most notable recent finding, which is very relevant to calorie restriction and was announced at almost the same time as my resveratrol post, is this:

Eat Less To Live Longer: Calorie Restriction Linked To Long Healthy Lives (9/26/07)
Now, reporting in the September 21 issue of the journal Cell, researchers from Harvard Medical School, in collaboration with scientists from Cornell Medical School and the National Institutes of Health, have discovered two genes in mammalian cells that act as gatekeepers for cellular longevity. When cells experience certain kinds of stress, such as caloric restriction, these genes rev up and help protect cells from diseases of aging.

"We've reason to believe now that these two genes may be potential drug targets for diseases associated with aging," says David Sinclair, associate professor of pathology at Harvard Medical School and senior author on the paper.

The new genes that Sinclair's group have discovered, in collaboration with Anthony Sauve of Cornell Medical School and Rafael de Cabo of NIH, are called SIRT3 and SIRT4. They are members of a larger class of genes called sirtuins. (Another gene belonging to this family, SIRT1, was shown last year to also have a powerful impact on longevity when stimulated by the red-wine molecule resveratrol.)

David Sinclair, of course, has been heavily involved in research on SIRT1 and resveratrol, as discussed here. He is also co-founder of Sirtris Pharmaceuticals, which is investigating drugs that target sirtuins. Sinclair is a former student of Leonard Guarente, who is also very prominent in sirtuin research, and who had a great deal to do with investigation of the analogous proteins in yeast and nematodes.

One of the most interesting things about the longevity-enhancing effects of sirtuin proteins in yeast and nematodes is that they seem to achieve their effects by rather different means. In yeast, one cause of aging is the formation of "ribosomal DNA circles", and SIR2 (under appropriate conditions) can inhibit this. In C. elegans, on the other hand, the biological effect that retards aging is the inhibition of "insulin signaling". So what is it that SIRT3 and SIRT4 do in the cells of humans (and other mammals)?
In this paper, the newly discovered role of SIRT3 and SIRT4 drives home something scientists have suspected for a long time: mitochondria are vital for sustaining the health and longevity of a cell.

Mitochondria, a kind of cellular organ that lives in the cytoplasm, are often considered to be the cell's battery packs. When mitochondria stability starts to wane, energy is drained out of the cell, and its days are numbered. In this paper, Sinclair and his collaborators discovered that SIRT3 and SIRT4 play a vital role in a longevity network that maintains the vitality of mitochondria and keeps cells healthy when they would otherwise die.

When cells undergo caloric restriction, signals sent in through the membrane activate a gene called NAMPT. As levels of NAMPT ramp up, a small molecule called NAD begins to amass in the mitochondria. This, in turn, causes the activity of enzymes created by the SIRT3 and SIRT4 genes--enzymes that live in the mitochondria--to increase as well. As a result, the mitochondria grow stronger, energy-output increases, and the cell's aging process slows down significantly.

Other news stories on this research:

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Failure of unique factorization

Monday, November 12, 2007

For previous posts in this series, see here.

In this installment we're going to look at a detailed example and discuss some fine points of factorization of algebraic integers. This will be a bit long and pedantic. However, all the reasoning is elementary, except for a small amount of Galois theory, which you can review here.

Let's look at an example where unique factorization fails. First, we need to introduce a concept that makes it easy to prove some results about factorization (and has many more applications as well). Suppose we have an algebraic number α∈F and F⊇ℚ is a Galois extension. (Such an extension always exists: it is a splitting field of an irreducible polynomial f(x) such that f(α)=0, but we don't necessarily assume F is the smallest such extension.) Let G=G(F/ℚ) be the Galois group.

To review a concept, which has been introduced before, we define the norm of α with respect to the extension F⊇ℚ to be the product of all numbers σ(α) as σ ranges over elements of G. (More generally, the norm works also for Galois extensions of base fields that contain ℚ.) Symbolically, the norm is:
NF/ℚ(α) = ∏σ∈G σ(α)
Note that "the" norm depends on the specific extension F/ℚ, and so the extension is indicated in the subscript.

For instance, let F=ℚ(√-5). F/ℚ is Galois, because it is the splitting field of the irreducible polynomial f(x) = x2+5 = 0. Any α∈F can be written as a+b√-5 for a,b∈ℚ. An element σ∈G can be specified by how it acts on a typical such element. Of course, since [F:ℚ]=2, G has only two elements: 1 (the identity) and σ, so σ is determined by how it acts on √-5. σ(√-5) has to be a root of f(x)=0 different from √-5, so it must be -√-5. It follows that σ(a+b√-5)=a-b√-5 for a,b∈ℚ, because σ is a field automorphism of F that leaves all elements of ℚ fixed. This should remind you of complex conjugation, because that is in fact the nontrivial automorphism of the group G(ℚ(i)/ℚ).

In the simple case at hand, we can give a simple formula for the norm:
NF/ℚ(a+b√-5) = (a+b√-5)(a-b√-5) = a2 + 5b2
(In the field ℚ(i), the norm of a complex number is the square of the modulus, i. e. |a+bi|2 = a2 + b2, so norm in the sense used here is closely related to the complex "norm".)

The norm symbol has some fairly obvious properties. From the way it is defined as a product, the norm is a group homomorphism from the multiplicative group of F to the multiplicative group of ℚ. It is also a homomorphism of the multiplicative semigroups of the rings of integers OF and ℤ, which means that the value of the norm of an algebraic integer is always an integer in the base field (in this case the integers ℤ of ℚ). This is because each σ∈G is a field automorphism which satisfies σ(αβ)=σ(α)σ(β) for all α,β∈F. In other words,
NF/ℚ(αβ) = NF/ℚ(α) NF/ℚ(β)
Furthermore, NF/ℚ(ε)=±1 if and only if ε is an invertible element of OF, i. e. a unit. (Since ±1 are the units of ℤ.)

Let's first determine the ring of integers OF. Let α=a+b√-5 be a general element of F, with a,b∈ℚ. If in fact α is an algebraic integer, then so is its conjugate α*=a-b√-5. Further, the sum α+α*=2a is in ℚ, and is also an algebraic integer, since the algebraic integers of an extension form a ring. But the only algebraic integers in ℚ are in fact in ℤ, so 2a∈ℤ. Similarly, 2b=(α-α*)/√-5 is an algebraic integer in ℚ, hence an element of ℤ, so 2b∈ℤ. The norm of both α and α* is a2+5b2, which is in ℤ. Multiplying the last expression by 4 shows (2a)2+(2b)25∈4ℤ. Since 5≡1 (mod 4), (2a)2+(2b)2≡0 (mod 4). This is impossible unless both 2a and 2b are even integers (just check the separate cases). Hence both a and b are in ℤ. The conclusion is that OF = {a+b√-5 | a,b∈ℤ}.

A slight elaboration of this argument shows that in any quadratic field ℚ(√d) where d∈ℤ is square-free, algebraic integers have the form OF = {a+b√d | a,b∈ℤ} unless d≡1 (mod 4), in which case OF = {(a+b√d)/2 | a,b∈ℤ, a≡b (mod 2)}. In other words, the naive guess that algebraic integers of ℚ(√d) just have the form a+b√d for a,b∈ℤ isn't entirely correct, but it is wrong only for d≡1 (mod 4), and then only by a little bit.

At this point, there is one delicate issue of nomenclature we must deal with. You will recall that a prime p∈ℤ is customarily defined as a (nonzero, nonunit) number which has no divisors other than units (±1) and ±p. We also proved that if p has this property, and if p divides a product mn, then either p divides m or p divides n (or maybe it divides both). In ℤ we can use this property to define p as a prime, since if the property is true of p then the more familiar condition that p has no nontrivial divisors is also true. This is because if p has this property, then the only divisors of p can be ±1 and ±p. (This follows from order properties of ℤ, because all divisors of a number n, except for ±n, have absolute values less than |n|.)

So these two properties of a nonzero p∈ℤ are equivalent. However, as we are about to see, the properties are not equivalent in other rings of integers. Nevertheless, we will find it convenient to use a generalization of the definition that p is prime if and only if p|mn implies p|m or p|m. So we will need a new term for the property of nonzero p that it is not a unit and not divisible by any other number except a unit times p. For this property we will use the term irreducible (like an irreducible polynomial). (And when this is the case, we say that p has only "trivial" factors, hence a nonunit p is defined to be irreducible if and only if all its factors are trivial, or equivalently if and only if it has no nontrivial factors.) We will make a similar distinction of "prime" and "irreducible" for integers α of other rings of integers.

Finally we can get back to factorization in F=ℚ(√-5). Observe that 21=3⋅7=(1+2√-5)(1-2√-5). We claim, first, that both 3 and 7 are irreducible in OF. Consider 3 first. If α=a+b√-5 were a nontrivial integral divisor of 3 – i. e. neither α nor 3/α is a unit – then we would have NF/ℚ(α) = a2+5b2 divides NF/ℚ(3) = 9. (Note, by the way, that for this extension, the norm is always nonnegative.) So NF/ℚ(α) must be either 3 or 9, since α isn't a unit. Obviously the equation a2+5b2=3 has no solutions for a,b∈ℤ. So NF/ℚ(α) isn't 3, hence it must be 9. Then NF/ℚ(3/α)=1, and 3/α is a unit, contrary to assumption. So 3 is irreducible. 7 is also irreducible, by a similar argument. The same kind of argument shows that 1±2√-5 must be irreducible, since both conjugates have norm 21, and any non-unit α that divided either would have a norm equal to 3 or 7, which we just observed is impossible. And we cannot have 1±2√-5 dividing either 3 or 7 (or vice versa), since 21∤9 and 21∤49.

What we've just shown is that 21 has two factorizations into irreducible numbers of Oℚ(√-5), and the factorizations are not equivalent, since the irreducible numbers in one factorization aren't unit multiples of either irreducible number in the other factorization. This shows that factorization of elements of the ring Oℚ(√-5) into irreducible numbers isn't unique.

This example shows that a number which has no non-trivial factors (e. g. 3 or 7) can divide a product (e. g. 21) of two other numbers (e. g. 1±2√-5) without dividing either one of the factors of the product. So an irreducible number is not "prime" in the sense that if it divides a product, it must divide at least one of the factors. This latter property is actually more useful in practice, so we want to use the term "prime" for it. Therefore, a distinction is made in a general ring of integers: a (nonzero, nonunit) number which has no non-trivial factors is said to be irreducible. (Equivalently, if α=βγ then either β or γ must be a unit.) On the other hand, the term prime is reserved for (nonzero, nonunit) numbers α which have the property α|βγ implies α|β or α|γ.

Now, in any ring of integers of an algebraic number field, a prime integer (in the new sense) must also be irreducible. This is because if α is not irreducible, then by definition we can write α=βγ, where neither factor is a unit. But if α is prime it must divide one of its factors. Say α divides β. Then β=αδ. Hence 1=δγ. That is, γ is a unit, contrary to assumption, and so α has only trivial factors, so it's irreducible. Thus the set of prime integers is a subset of the set of irreducible integers.

However, in the example we just examined where F=ℚ(√-5), where we do not have unique factorization, then some irreducible numbers are not prime. E. g. 1+2√-5 is irreducible (as we showed), but it is not prime, because it divides 21, but does not divide either 3 or 7. Therefore it's possible for the set of prime integers to be a proper subset of the set of irreducible integers, i. e. a strictly smaller subset.

This raises some interesting questions. Recall that the cases we are interested in are the rings of algebraic numbers. By definition, these are the rings of integers A=OF of a finite extension F/ℚ.

In any such A, it is always true that we can write any element as a product of a finite number of irreducible integers. The reason is that for any (nonzero, nonunit) α∈A, if α isn't irreducible, we can write α=βγ, where neither factor is 0 or a unit. Since F/ℚ is a finite extension, we can always compute norms, and we have NF/ℚ(α) = NF/ℚ(β)NF/ℚ(γ). In some extensions a norm can be negative, but we can also stick in the absolute values of each term, and since no term is ±1, each factor on the right hand side is an an integer in ℤ that is strictly smaller in absolute value than |NF/ℚ(α)|. Since all numbers here are finite, this process can't continue indefinitely. So not only do we get a finite product of irreducible integers, but we in fact get a finite product of finite powers of distinct irreducible integers. However, as the example above showed, this factorization need not be unique.

On the other hand, we can also say that if some algebraic integer α can be expressed as a product of powers of distinct prime integers, then (up to order and unit factors), the expression is unique as to which primes occur in the factorization and the powers of each that occur. To prove this, note first that any prime π which appears in one factorization into powers of primes must appear in the other. Because since π is in one factorization, it divides α, and because it is prime, it must divide at least one factor in any other factorization into powers of distinct primes. That factor must then be a power of π, since π can't divide a power of a different prime (using the fact that all primes are irreducible). Furthermore, if π occurs at all in some factorization of α, it must occur to eactly the same power in each factorization. Otherwise if the smaller power has exponent n, then we could cancel πn from both factorizations. That would leave the integer α/πn with distinct prime power factorizations, one containing π and the other not, which we just ruled out.

The problem here is that we do not know that every integer α∈A actually has even one factorization into distinct primes. Consequently, if there can be irreducible integers of A that aren't prime, so the set of prime integers is a proper subset of the set of irreducible integers, we cannot be sure that there is the kind of unique factorization theorem for integers of A that we have for ℤ, regardless of whether we specify "primes" or "irreducibles". Factorizations into irreducibles can't be guaranteed to be unique, while factorizations into only powers of primes might not even exist.

However, if the set of primes is the same as the set of irreducibles, then factorizations of any integer of A into irreducibles, and hence primes, are guaranteed to exist, And furthermore, the factorizations must also be unique.

What about converses? Suppose we can guarantee that factorizations of any α∈A into primes must exist. Does that imply prime = irreducible? Yes, for the following simple reason. We have already shown that if a factorization into primes exists, it must be unique. So suppose α is irreducible. If a factorization into primes must exist, then α=πβ for some prime π. But because α is irreducible, β has to be a unit. Any prime times a unit is still a prime, so α itself is a prime, and the set of irreducible elements contains only primes.

Or suppose we can guarantee that factorizations of any α∈A into irreducibles are unique. Does that imply prime = irreducible? Again the answer is yes. For suppose α is irreducible and that for some β and γ we have α|βγ. Since α|βγ there is a δ such that αδ = βγ. Write the right and left hand sides as a product of powers of distinct irreducible numbers, so that (ignoring possible factors which are units) αδ1⋅⋅⋅δm = β1⋅⋅⋅βn (except that if α is among the δi, combine the terms). Then by the assumed uniqueness αk = βj for some j and some power k≥1, and both sides are powers of the same irreducible number α. That number must have been a divisor of either β or γ (or both). In any case, this means α is prime.

What we have now proven is this: If A=OF is the ring of integers of a finite extension F/ℚ, the following conditions are equivalent:
  1. The set of irreducible elements of A is the same as the set of prime elements of A (up to unit factors).
  2. Every element of A has a unique factorization into powers of irreducible elements (up to unit factors).
  3. Every element of A has a unique factorization into powers of prime elements (up to unit factors).

So (as is obvious) if all irreducible elements are prime, the difference in how these are defined is irrelevant. However, if there are irreducible elements that aren't prime, then factorizations of some integers into powers of irreducibles will not be unique, and some integers will not even have a factorization into powers of primes.

It turns out that there are certain types of rings in which all irreducible elements are prime, so the two concepts are equivalent in such rings. ℤ is one example of such a ring, but it is not the only one. Certainly, if we could guarantee that the integers of some extension of ℚ always had some factorization into primes (in the special sense used here), then as we showed, the factorizations must be unique. In order to investigate this issue further, we need help from the theory of ideals of rings of integers. By placing certain conditions on the types of ideals that the ring can have, we will be able to guarantee that any irreducible integer is prime, so that factorizations of any integers into irreducibles (which always exist) are also factorizations into primes, and therefore that they are unique.

One important type of ring that has this property is called a principal ideal domain, which means that every ideal consists of elements that are multiples of a single element (that isn't a unit) by some element of the ring. This is in fact the case with ℤ, where all ideals are of the form nℤ for some n. (The ideal is the full ring ℤ itself if n=±1.) But there are other rings of integers that are also principal ideal domaings, and a large part of algebraic number theory is about identifying which rings have this property. We'll look into this in much more detail, but first we need to explain further why we care about unique factorization.

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The religious right is wrong again

Sunday, November 11, 2007

Here's a cheery follow-up of more news of the sort in this earlier post.

Report: Abstinence Not Curbing Teen Sex
Programs that focus exclusively on abstinence have not been shown to affect teenager sexual behavior, although they are eligible for tens of millions of dollars in federal grants, according to a study released by a nonpartisan group that seeks to reduce teen pregnancies.

"At present there does not exist any strong evidence that any abstinence program delays the initiation of sex, hastens the return to abstinence or reduces the number of sexual partners" among teenagers, the study concluded.

The report, which was based on a review of research into teenager sexual behavior, was being released Wednesday by the nonpartisan National Campaign to Prevent Teen and Unplanned Pregnancy.

The study found that while abstinence-only efforts appear to have little positive impact, more comprehensive sex education programs were having "positive outcomes" including teenagers "delaying the initiation of sex, reducing the frequency of sex, reducing the number of sexual partners and increasing condom or contraceptive use."

Sadly, some Congressional facilitators of the religious right want to waste more of our tax money ($141 million) on more of this same sort of tax-sponsored religious propaganda:
A spending bill before Congress for the Department of Health and Human Services would provide $141 million in assistance for community-based, abstinence-only sex education programs, $4 million more than what President Bush had requested.

Contact your Congressperson and complain.

And incidentally, not only do abstinence-only programs not work, they are based on misinformation and myths about comprehensive sex education:
The study, conducted by Douglas Kirby, a senior research scientist at ETR Associates, also sought to debunk what the report called "myths propagated by abstinence-only advocates" including: that comprehensive sex education promotes promiscuity, hastens the initiative of sex or increases its frequency, and sends a confusing message to adolescents.

None of these was found to be accurate, Kirby wrote.

Instead, he wrote, such programs [i.e. comprehensive sex education] improved teens' knowledge about the risks and consequences of pregnancy and sexually transmitted diseases and gave them greater "confidence in their ability to say 'no' to unwanted sex."

Additional information:

Emerging Answers 2007

National Campaign to Prevent Teen and Unplanned Pregnancy


Religion and war

Friday, November 9, 2007

People bitch a lot about violence featured in movies and TV, but ignore a worse problem – how the sort of real (not make-believe) violence known as war is often associated with religion.

Now there may be a better theoretical understanding of how and why this association between religion and war may exist. Two articles in the October 26, 2007 issue of Science discuss evolutionary simulations which show that war drives the joint evolution of altruism and hostility to outsiders. Based on (but going beyond) this work, we will see how religion may be associated with warfare.

The first "perspectives" article gives an overview:

The Sharp End of Altruism
Which would you prefer: a society of selfish but tolerant freetraders, or a warrior society in which people help one another but are hostile to outsiders? If you value both altruism and tolerance, neither seems ideal. Societies of tolerant altruists, however, are exceedingly rare in the simulation presented by Choi and Bowles on page 636 of this issue. Instead, altruism flourishes only in the company of outgroup hostility (parochialism), with war as both the engine of this coevolutionary process and its legacy. For a compatriot, the parochial altruist who risks his life is a shining knight, whereas the outsider encounters the sharp end of this altruism.

The second article is a technical presentation of the research itself, which was the work of Jung-Kyoo Choi and Samuel Bowles:

The Coevolution of Parochial Altruism and War
Altruism—benefiting fellow group members at a cost to oneself—and parochialism—hostility toward individuals not of one's own ethnic, racial, or other group—are common human behaviors. The intersection of the two—which we term "parochial altruism"—is puzzling from an evolutionary perspective because altruistic or parochial behavior reduces one's payoffs by comparison to what one would gain by eschewing these behaviors. But parochial altruism could have evolved if parochialism promoted intergroup hostilities and the combination of altruism and parochialism contributed to success in these conflicts. Our game-theoretic analysis and agent-based simulations show that under conditions likely to have been experienced by late Pleistocene and early Holocene humans, neither parochialism nor altruism would have been viable singly, but by promoting group conflict, they could have evolved jointly.

Unfortunately, both articles require a subscription for access.

Curiously, there appears to have been almost no reporting on this research in the usual places that report on scientific research for a general audience. (Wonder why that is....) And this is even though the Santa Fe Institute, with which one of the researchers (Bowles) is associated, did put out this press release:

The coevolution of parochial altruism and war
In "The Coevolution of Parochial Altruism and War" appearing in the October 26 issue of Science, SFI researcher Samuel Bowles and colleague Jung-Kyoo Choi of Kyungpook National University in South Korea suggest that the altruistic and warlike aspects of human nature may have a common origin.

Altruism – benefiting fellow group members at a cost to oneself – and parochialism – hostility toward individuals not of one's own ethnic, racial, or other group – are common to human nature, but we don't immediately think of them as working together hand in hand. In fact the unexpected combination of these two behaviors may have enabled the survival of each trait according to Bowles and Choi.

They show that the two behaviors – which they term "parochial altruism" – may have in fact coevolved. On the face of it joining parochialism to altruism is puzzling from an evolutionary perspective because both behaviors reduce one's payoffs by comparison to what one would gain by avoiding them. Aggression consumes resources and risks death; altruism, particularly toward those with whom we have no direct relationship, has the effect of helping other genes advance at our expense. But parochial altruism could have evolved if parochialism promoted intergroup hostilities and the combination of altruism and parochialism contributed to the success of these conflicts.

Using game theoretic analysis and agent-based simulations Bowles and Choi show that under conditions likely to have been experienced by late Pleistocene and early Holocene humans neither parochialsim nor altruism would have been viable singly, but by promoting group conflict, they could have evolved jointly.

"But even if a parochial form of altruism may be our legacy," said Bowles, "it need not be our fate." He pointed to the many examples of contemporary altruism extending beyond group boundaries, and the fact that hostility toward outsiders is often redirected or eliminated entirely in a matter of years.

Now, none of this actually mentions religion. Choi and Bowles don't discuss it. So where does religion come into it? We'll get to that shortly. But first, let's review a bit about how altruism and cooperation in human cultures are thought to have evolved.

At first, it could seem that altruism and cooperation are unlikely to have evolved in humans at all, because they seem to be traits of an individual that are of more benefit to others than to the individual who happens to possess them.

However, there is a long history of evolutionary studies that have suggested how tendencies toward altruism and cooperation could have evolved in human groups. For example, starting in 1964 William D. Hamilton argued that altruism toward blood relatives helped to favor shared genes that fostered such altruism. This was termed "kin altruism".

Additional scientific consideration of the evolution of morality, altruism, and cooperation took off in the 1970s, in the work of people like Robert Trivers and Robert Axelrod. Using game theoretic arguments and simulations they showed how another type of altruism – "reciprocal altruism" – could arise in populations where individuals interacted frequently and could learn which others had earned a reputation for dependability in their dealings with other group members.

Many, many others have written on the subject since then, such as Edward O. Wilson (e. g. Consilience, published in 1998), and Steven Pinker (How the Mind Works, published in 1997). A very good history of the subject up until 1996 can be found in Matt Ridley's The Origins of Virtue.

On the other hand, in spite of arguments advanced showing the benefits to individuals of practicing altruism within a single tribe or cultural group, the fact remains that separate, unrelated groups could easily come into conflict over access to resources (e. g. water, game, other food sources, etc.), especially in times of scarcity due to overpopulation, unfavorable climate, etc. The result would be warfare.

Many people have also studied how evolutionary tendencies have contributed to aggression and warlike behavior between competing human groups. It seems that separate groups that have relatively low genetic similarity to each other and must compete for scarce resources have a notable tendency to come into conflict with each other, and to solve their problems of overpopulation or resource scarcity by killing as many members of the other group as possible. A good exposition of such ideas can be found in this article by Keith Henson: Evolutionary Psychology, Memes and the Origin of War.

It seems very reasonable to see such considerations as the source of the very human tendency to exhibit distrust and even hostility towards other humans who are noticeably "different", especially in physical characteristics, but also when there are simply cultural differences in taste, belief systems, etc.

Furthermore, when conflict between groups does occur and takes the form of open warfare, there is a distinct advantage for groups that have a high percentage of individuals who behave altruistically and cooperatively with each other. If you accept the (somewhat controversial) notion of evolutionary "group selection", this fact provides yet another evolutionary argument for the development of a third type of altruism – parochial altruism – within groups – because groups with the higher percentage of members who cooperate with each other will tend to prevail.

However, there is another side to this story. Individuals will not entirely lose a tendency to gain personal advantage through selfish behavior (such as hoarding food). Altruism can be disadvantageous for an individual if it goes too far, so there is some evolutionary pressure against it also. In an environment where scarcity of resources is not a large problem, individuals can serve their own interests by being open to interaction with members of other groups – especially for commerce and trading of "excess" goods. Individuals who are selfishly willing to trade their goods with members of other groups for the best exchange they can achieve will tend to do better for themselves since they are willing to "sell" to the highest bidder, regardless of group membership.

This, then, is the setting on which Choi and Bowles based their simulation. They considered two kinds of traits an individual could have. One related to altruism (A) vs. selfishness (N, for "not altruistic"). The other related to tolerance (T) vs. hostility (P, for "parochial") towards member of other groups. Any given individual could have one of four possible combinations (AT, AP, NT, NP). They started with groups having members with differing proportions of each possible combination.

Absent intergroup conflict, NT individuals (the most tolerant but selfish) tend to be most successful, and AP the least successful. But when intergroup conflicts occur, groups with the most AP types do better than groups with the most NT types. The simulations proceeded over thousands of generations, and a variety of parameters, all believed to be consistent with what is known about late Pleistocene hunter-gatherer human tribes, were tested.

The net result was that groups with many NT or AP individuals can both be successful, depending on how much warfare occurs (which depends on environmental conditions). But in most cases, groups with high proportions of NP or AT individuals lose out under any conditions. So one conclusion is that in order to have a lot of altruism within a group, you have to expect a lot of parochial intergroup hostility. Conversely, in order to have groups with a lot of tolerance towards other groups, you should expect less altruism and cooperation within the group. Choi and Bowles maintain that the same results tend to arise from a wide variety of different initial conditions.

True, this is "only" a simulation study. And it rests on the assumption that altruism and parochialism (or their opposites) are heritable traits (which alternatively might be transmitted culturally rather than genetically). But it seems to give results that accord well with what we know of human history. And that's where religion enters the picture. (Choi and Bowles do not discuss religion, so what follows is based on their findings, but also the contributions of others.)

In evolutionary terms, why is it that religion is so widespread in human societies? There are a variety of plausible explanations. One is that religion provides the rationale for moral and ethical principles that promote intergroup cooperation and altruism. The argument made by supporters of this idea – such as David Sloan Wilson in his book Darwin's Cathedral: Evolution, Religion, and the Nature of Society – is that societies and cultures with strong religion-based ethical and moral principles have a competitive advantage over other groups.

However, what the Choi-Bowles simulation suggests is that this advantage is realized only when groups often engage in conflict and war. For otherwise, there is an advantage for groups with lots of tolerance towards other groups, and lots of free-traders working for their own self-interest.

So, ironically, religion may have developed as a result of intergroup warfare, as a social artifact that helps justify intragroup altruism that actually was selected for because of the warfare. And at the same time, religion would also incorporate a justification for the intergroup hostility and aggression that arose from the same evolutionary process.

In other words, evolutionary pressures tend to bring about an association of religion and warfare. Note that this is not saying religion "causes" war. Indeed, evolutionary theory suggests that overpopulation and resource limits usually tend to be what "causes" war. But when such conditions prevail, it isn't too surprising to find a close association between religion and war. Just recall the slogan some religious believers are so fond of: "There are no atheists in foxholes." (In other words, most of the cannon fodder found in foxholes and military cemeteries is (or was) religious believers.)

Of course, most religions aren't pro-war full time. Many religious believers oppose war because of their faith. Nevertheless, most religions have their holy warriors, such as Mujahideen and Crusaders. (Military equipment of predominantly Christian nations is sometimes named a Crusader.) Most religions have their own versions of Onward Christian Soldiers. And most religions celebrate war in other ways.

But is there scientific evidence of a relation between religion and war? Yes. Consider this:

When God Sanctions Violence, Believers Act More Aggressively
Reading violent scriptures increases aggressive behavior, especially among believers, a new study finds. The study by University of Michigan social psychologist Brad Bushman and colleagues helps to illuminate one of the ways that violence and behavior are linked.

"To justify their actions, violent people often claim that God has sanctioned their behavior," said Bushman, faculty associate at the U-M Institute for Social Research and lead author of the article published in the March 2007 issue of Psychological Science. "Christian extremists, Jewish reactionaries and Islamic fundamentalists all can cite scriptures that seem to encourage or at least support aggression against unbelievers."

To be sure, this is hardly a new observation. Mark Twain, as well as many others before him, had already nailed it.

Update (11/13/07): I see that I missed one of the U. S. military's pricey toys proposed artillery systems (which was canceled in 2002) that used the "Crusader" moniker – the Crusader 155mm Self-Propelled Howiter. See here or here. Onward, Christian soldiers, indeed.

Massive Star's Afterlife: A Supernova Seeds New Planets

Tuesday, November 6, 2007

Massive Star's Afterlife: A Supernova Seeds New Planets
A spectacular new image shows how complex a star's afterlife can be. By studying the details of this image made from a long observation by NASA's Chandra X-ray Observatory, astronomers can better understand how some stars die and disperse elements like oxygen into the next generation of stars and planets.

At a distance of about 20,000 light years, G292.0+1.8 is one of only three supernova remnants in the Milky Way known to contain large amounts of oxygen. The image shows a rapidly expanding, intricately structured, debris field that contains, along with oxygen, other elements such as neon and silicon that were forged in the star before it exploded.

Supernova remnant G292.0+1.8 – click for 792×792 image

More: here

When The Going Gets Tough, Maybe You Should Quit

This caught my eye, because of the connection with "stress", as discussed here and here:

When The Going Gets Tough, Maybe You Should Quit
Are there times when it is better to simply give up? Psychologists have been exploring this question, and more specifically a possible link between tenacity and both physical and mental health.

It would seem that persistence would be tonic over the long haul; hanging tough should increase the odds that you’ll succeed, and personal success is closely linked to well-being. But what if the goal is extremely unlikely? When does an admirable trait like perseverance start to look more like beating your head against the wall?

To test this in the laboratory, psychologists Gregory Miller and Carsten Wrosch developed a psychological instrument that can reliably distinguish between people who when faced with a difficult goal either persist or let go of it. In a series of experiments, the psychologists exhaustively studied these two personality types to see how healthy and well adjusted they are.

In their most recent study, published in the September issue of Psychological Science, a journal of the Association for Psychological Science, the psychologists followed teenagers for a full year. Over that time, individuals who did not persist obtaining hard to reach goals had much lower levels of a protein called CRP [C-reactive protein], an indicator of bodily inflammation. Inflammation has recently been linked to several serious diseases, including diabetes and heart disease.

Well, is it really surprising that there are health benefits associated with having a more easy going, "laid back" personality?

There's a very good book that delves into this in great detail – Why Zebras Don't Get Ulcers, by Stanford professor Robert Sapolsky. (Quick summary is here.)

And while we're on the subject, there's this press release that just came out:

Relationship Between Environmental Stress And Cancer Elucidated

One way environmental stress causes cancer is by reducing the activity level of an enzyme that causes cell death, researchers say.

They found that stress-inducing agents, such as oxidative stress, recruit a protein called SENP1 that cuts a regulator called SUMO1 away from the enzyme SIRT1 so its activity level drops, says Dr. Yonghua Yang, postdoctoral fellow in the laboratory of Dr. Kapil Bhalla, director of the MCG Cancer Center.

This fundamental finding about the relationship between stress and cancer opens the door for treatments that increase SENP1 activity, making it easier for cells that are becoming cancerous to die.

In yet another example of how deeply interrelated different biological processes are, it's worth noting that SIRT1 is a HDAC enzyme, whose activity seems to be enhanced by both resveratrol and calorie restriction. By mechanisms that are still somewhat mysterious, this in turn may be beneficial for longevity. If indeed oxidative stress has the effect of decreasing SIRT1 activity and hence promoting cancer, this may help explain at least some of the longevity benefit of SIRT1.

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Readings: Cosmology and astrophysics, 4 November 2007

Sunday, November 4, 2007

The text following each item is quoted material, except for editorial comments, which are in color.

FSU physicist shining a light on mysterious 'dark matter'
"Recent scientific breakthroughs have shown that most of the matter in the universe—about four-fifths—is not made up of atoms, but of something else, called 'dark matter,'" said Howard Baer, FSU's J.D. Kimel Professor of Physics. "The evidence for dark matter is now overwhelming, and the required amount of dark matter is becoming precisely known." ...

A theoretical physicist, Baer employs mathematical models and calculations, as opposed to experimental methods, in an attempt to understand the basic properties of dark matter. To that end, he travels frequently to CERN, the world's largest particle physics laboratory, located on the border between France and Switzerland. At CERN, teams of physicists from all over the world are preparing for the start-up of what will be the world's most powerful particle accelerator, the Large Hadron Collider (LHC), in 2008. With the LHC, they will conduct experiments that seek to solve some of the fundamental mysteries of science, including the identity of dark matter. In addition to searches at the LHC, the hunt for dark matter is progressing at experiments deep underground in Minnesota, under thick Antarctic ice, and even in outer space.

Another piece in the dark matter puzzle
“We took one specific theory about dark matter,” Riemer-Sørensen explains. “We look at a specific type of decaying particles, and if they represent dark matter, they will decay and transform into photons in x-rays.” The particles in question are axions, hypothetical elementary particles used in theories describing “extra” dimensions. The idea, she says, is to look for an area of the universe that has a great deal of dark matter, and then look for weak x-ray emissions. ...

So, did Riemer-Sørensen and her colleagues find the weak dark matter x-ray emissions? “We didn’t find any clear signs of x-ray emissions from axions in these regions,” she says. “And that tells us something about dark matter.” If dark matter particles do follow the reactions of decay set forth in the theory of axions as dark matter, then dark matter has an extraordinarily long lifetime. “If dark matter does decay,” Riemer-Sørensen insists, “then the lifetime of the axions is at least three million billion years, which is twenty thousand times longer than the lifetime of the universe.”

Can this experiment identify dark matter?
“Many experiments and observations all point to the existence of some form of matter that is different from the ordinary matter that makes up starts, planets and even people,” Bertone explains. Because dark matter is so prevalent in the universe, many scientists are interested in better understanding its role in fundamental physics, as well as the formation of the universe. “There are efforts to clarify the nature of dark matter.”

Bertone explains that there are three main approaches to detecting dark matter particles, which are likely to be weakly interacting massive particles (WIMPs). The first, he says, is an earthbound method using particle accelerators, like the Large Hadron Collider due to go online at CERN next year. “Scientists hope to find particles in accelerators that could be like the dark matter found in the rest of the universe.”

The next method of detection is one of indirect observation. Looking out into space, Bertone says, scientists “look for some signal due to interaction of particles amongst themselves.”

The strategy set forth in the article belongs to the third approach, which is to build a large detector and wait for a dark matter particle to interact with ordinary matter. “To show the power of this technique, we focused on an experiment called COUPP [Chicagoland Observatory for Underground Particle Physics]” Bertone says. “It is a bubble chamber, much like what has been used before in other fields.”

In the dark: science still mystified by stuff of universe
Most of the universe -- 96 percent, to be exact -- is made of dark matter and energy whose composition we simply do not fathom, a Nobel laureate told physicists gathered this week to explore the intersection of the infinitely small and the infinitely large. ...

Most physicist attending the conference here on astroparticle physics think the basic ingredient is probably some as-yet undiscovered elementary particle, a relic of the "Big Bang" that created the Universe around 13 billion years ago.

The favored candidate is the neutralino, a "supersymmetric" particle whose existence has yet to be proven. But the hunt in underway, using both direct and indirect methods, including experiments to be conducted at the Large Hadron Collider (LHC) in Switzerland.

Over the next decade, explained Katsanevas, scientists will be tackling three big questions besides dark matter: the origin of cosmic rays, the existence of gravitational waves, and the mass of neutrinos, which have provided the first solid evidence of phenomena beyond what is called the Standard Model of particle physics.

Astronomers Aim to Shine Light on Universe's 'Dark Energy'
In nearly a decade since it was discovered, a mysterious cosmic feature dubbed "dark energy" has lain like a downed redwood across the path of scientists trying to reach the holy grail of physics – a fundamental theory of matter and its basic forces. ...

"After about 10 years it's clear [dark energy] is not going away.... We have to really figure out what this is," Riess says. The past decade also has shown that "dark energy lives at the crossroads of two of our best theories of physics: quantum mechanics and general relativity."

A successful marriage of quantum theory and gravity is the last major hurdle in demonstrating that the basic four forces of nature – gravity, electromagnetism, and weak and strong forces that operate at the subatomic level – are manifestations of a single force that dominated the universe in the first few fractions of a second after the big bang. With dark energy, "nature is giving us a hint of how it does quantum gravity," Riess says.

Hubble Telescope: Solved and Unsolved Mysteries
Beyond snapping extraordinary pictures of faraway nebulas, the revolutionary Hubble Space Telescope has completely transformed our view of the universe since it was launched in 1990. By capturing the clearest, deepest images of the cosmos ever, Hubble has shed light on some long-standing mysteries perplexing scientists-while uncovering far deeper ones that have yet to be solved. ...

Dark energy has prompted new theories regarding the origin of the universe, such as one where clashing membranes of reality trigger endless cycles of cosmic death and rebirth, as well as the fate of the universe, raising the possibility that dark energy ends the universe in a Big Rip. Future progress on understanding dark energy's nature will likely require a dedicated dark energy space mission, "for sometime in the middle of the next decade, perhaps," Leckrone said.

The other mysteries mentioned in the article involve dark matter, gamma-ray bursts, direct imaging of extrasolar planets, and protoplanetary disks. These are all issues which can be studied by more or less conventional optical or infrared telescopes – much like Hubble, only more powerful. There is also a need for a more powerful ultraviolet-sensitive telescope, which is not currently even part of NASA's agenda. Although the descriptions of the "mysteries" in the article are sketchy, there are links to additional information.

Is the universe a doughnut?
Later work by Neil Cornish of Case Western University, David Spergel of Princeton University, and Glenn Starkman of the University of Maryland extended this technique to consider a wider range of possible topologies. Such a method has been applied to the WMAP results, examining the possibility that it could have a complex topology— not a toroid perhaps, but rather a dodecahedron (a bit like a soccer ball, but with all sides equivalent in size and shape). Although preliminary data (analysed in 2003) seemed to rule out this model, more recent looks at the WMAP findings have revived the idea that if you venture far enough out into space you'll return to your starting point. Hence Homer's doughnut theory may have at least a sprinkling of truth: the universe could indeed have loops.

This is a pretty good article for an overview of the shape of the universe, in spite of its facetious premise (that a cartoon world can be effectively used to explain highly technical cosmology). The genre, of popular TV shows used as points of embarcation into explanations of scientific topics, is growing. First there was The Physics of Star Trek, which is not too surprising a connection. But The Physics of the Buffyverse? And now, in effect, physics according to Homer Simpson? Having read only the first of these, I don't know that these aren't all quite good books. But what this trend says about our culture... I don't really want to go there.

However, if Robert Gilmore can write physics books based on such metaphorical worlds as those of Alice in Wonderland, The Wizard of Oz, A Christmas Carol, or Grimms' Fairy Tales, ... well, why not? Perhaps we need someone to write books of physics based on The Odyssey or The Divine Comedy? And while we're at it, let's not leave out the physics of the Niebelungenlied and the Mahabharata. I can hardly wait.

Why the Universe is All History
Some galaxies are so remote that their light hasn't had sufficient time to reach us yet, despite about 13.7 billion years of travel. There could also be more distant objects that will forever remain unknown to us.

"Because the universe is expanding and the expansion appears to be accelerating, there may be distant galaxies which if we can't see them now because their light has not had time to reach us, we will never see," Stecker said.

So we can never see the universe as it is, only as it was at various stages of its development.

New-School 'Aether' May Shed Light on Neutron Stars
Among scientists, it is widely believed that there is no such thing as an aether – a medium pervading all space that allows light waves to propagate, similar to how sound needs air or water – but a part of its spirit may live on. A group of University of Maryland (UM) physicists have proposed a modern spin on the aether of old and have used it to make new predictions about the behavior of neutron stars. ...

The UM researchers – Christopher Eling, Ted Jacobson, and Coleman Miller – describe their aether as a preferred state of rest at each point of spacetime. This preferred state would not be the result of something known, such as a gravitational field or cosmic background radiation, but may, they say, arise from the structure of empty space in quantum gravity theory. ...

The UM team use the new aether to make concrete predictions about neutron stars that differ from those generated by general relativity, Einstein’s theory of gravity. The group's calculations show that the maximum mass of neutron stars would be smaller than in general relativity and the increase in wavelength, or “redshift,” experienced by photons emitted from the stars' surfaces must be 10 percent larger.

Predicting Planets
Discovering new planets that orbit distant stars has become commonplace. But now a team of astronomers has managed to predict the orbit of an extrasolar planet — before anyone knew for certain that it existed. The last time that happened was more than 150 years ago. ...

The more-recently discovered planet is known by a rather-less-elegant name: HD 74156d. It is a gas giant, slightly more massive than Saturn, orbiting a sun-like star about 65 parsecs (212 light-years) away. Its orbit was predicted in 2004 by Rory Barnes and Sean Raymond, theoretical astronomers then at the University of Washington in Seattle. Three years later, Jacob Bean, an astronomer now at the Georg-August-Universitaet in Goettingen, Germany, announced that he had found the planet, pretty much where Barnes and Raymond said it would be.

Lonely Planets of the Cosmos
A brief letter in Nature was John Debes's inspiration. The 1999 piece, by David J. Stevenson (Caltech), proposed that planets with liquid water oceans — and even life — could exist in the cold, dark depths of interstellar space far from any star. Based on the knowledge that some fraction of planets must get gravitationally ejected from their systems during the systems' formation, the paper theorized that some of these ejected planets could, with enough internal heat, keep their atmospheres and stay warm enough to support liquid water below a thick frozen crust.

What might happen if such an outcast had a big moon? To find out, Debes (at the Carnegie Institution of Washington) ran 2,700 computer simulations based on an Earth-mass planet and a lunar-mass companion.

The Enduring Mysteries of the Sun
The sun lies at the heart of our solar system, but it still holds back many secrets from science. Unlocking these mysteries could shed light on puzzling activity seen in other stars and even safeguard lives.

It's surprising how much we don't understand about stars – from either theory or observation – considering that we live so close to one.

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