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A new study involving lab mice could bring a breakthrough in treating Alzheimer's. Image courtesy of Flickr user Rick Eh?

Alzheimer’s disease damages brain tissue in a variety of ways, but one of the most important seems to be the buildup of “plaques.” The deposits contain protein called beta-amyloid. Normally, beta-amyloid is produced and then removed at a more or less constant rate, but not in individuals with Alzheimer’s disease.

Beta-amyloid is normally removed from the brain with the help of a molecule called apolipoprotein. One version of this molecule, ApoE, increases a person’s risk of Alzheimer’s and appears to be linked to beta-amyloid buildup.

Meanwhile there is bexarotene, a chemical used in cancer treatments (officially for cutaneous T-cell lymphoma but unofficially for some other cancers). Researchers at Case Western Reserve University School of Medicine used bexarotene in mice that have a condition similar to human Alzheimer’s to change the relationship between ApoE and beta-amyloid. The drug caused plaques to be removed from much of the neural tissue. The behaviors of the mice on learning and memory tasks also changed in ways indicating that the effects of the Alzheimer’s-like condition was reversed, at least partially. A mere 72 hours of treatment with bexarotene “cured” misdirected nesting behavior and caused improvement in other tasks. Olfactory sense improved in some of the mice over a nine-day period.

There are reasons to be very positive about this result, but also reasons to be very cautious. Among the reasons to be cautious are:

• Mice are not humans, so there may be important but subtle differences in brain chemistry that will cause this treatment to not work the same way in humans.
• Although mice improved behaviorally, it is difficult to match mouse and human forms of “dementia,” so we must be cautious in interpreting the meaning of improvement in the mice.
• As far as I can tell, the effects of this treatment may be only short-term. Even though bexarotene has been used widely on humans, the dose and treatment approach needed for addressing human Alzheimer’s may be very different. It could even be dangerous or implausible.
• The ApoE contribution to Alzheimer’s is only one part of the disease. It may well be that the best-case scenario of a treatment based on this research would be only a partial cure, or only for some individuals.

Reasons to be optimistic include:

• The result seen in the mice was dramatic and fast. Half the plaques were removed in 72 hours, and over the long term, 75 percent were removed.
• Bexarotene is a drug already approved for use (in other areas of treatment) by the FDA, so the process of investigating this drug’s efficacy and safety is much more advanced than if it was some chemical not previously used on humans.
• Even if it turns out that this drug will not be usable on humans to treat this condition, a result like this strongly indicates a path for further research to develop similar treatments.

The researchers are optimistic. Paige Cramer, first author of the study, noted in a press release, “This is an unprecedented finding. Previously, the best existing treatment for Alzheimer’s disease in mice required several months to reduce plaque in the brain. Research team leader Gary Landreth notes that “this is a particularly exciting and rewarding study because of the new science we have discovered and the potential promise of a therapy for Alzheimer’s disease. We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment.”

A lot of research related to disease seems to be reported in press releases and elsewhere with more optimism than deserved, but in my opinion this is a case where the new research is more closely linked to potential treatment than is often the case. Keep an eye on this story!

Cramer, Paige E. John R. Cirrito, Daniel W. Wesson, C. Y. Daniel Lee, J. Colleen Karlo, Adriana E. Zinn, Brad T.
Casali, Jessica L. Restivo, Whitney D. Goebel, Michael J. James, Kurt R. Brunden, Donald A. Wilson, Gary E. Landreth. (2012). ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD
Mouse Models. Science. Science Express 9 February 2012. DOI: 10.1126/science.1217697

A fruit fly. Image by Flickr user *dougmino*

Gravity potentially affects all biological processes on Earth, even though this may be hard to believe while we watch flies walking around on our ceilings as though gravity did not matter to them at all. Of course, gravity is only one factor, and other factors such as adhesion or buoyancy determine whether an organism falls off the ceiling, say, or how long it takes an organism to settle to the ground.

We’ve known for a long time that humans are harmed by long periods in low-gravity environments. Astronauts return from space with muscle atrophy and reduced bone mass. These effects seem to get worse over time, so understanding the effects of gravity on human physiology is essential when planning long-distance space flights. Studying the effects of low gravity in space craft and space stations is expensive. Anyone who has spent time working in a laboratory knows that many experiments have to be redone numerous times just to get the procedures to work properly. If a key step in carrying out an experiment on, say, the response of cells to lack of gravity, is “shoot the experiment into space and keep it there for two months” then it will take a very long time and a lot of money to get results one might need to make sense of low-gravity biology. Therefore, it would be nice to have an anti-gravity machine in our Earth-bound laboratories to run experiments without the cost and scheduling constraints imposed by space flight.

There is a way to simulate weightlessness at a small scale in the lab. A team of researchers from several European institutions have used magnetism to offset the effects of gravity at the cellular level. The method is called diamagnetic levitation. (Another method for simulating anti-gravity uses a “Random Positioning Machine” (RPM).)  Some materials—diamagnetic materials—are repelled by a magnetic field. Water and most biological tissues fall into this category. A very powerful magnetic field can be applied to these tissues to offset the effects of gravity, so molecules moving about and doing their thing inside cells do so as though there were no gravity acting on them. According to a recent study, it appears that gene expression is affected by gravity. (The paper is published in BMC Genomics and is available here.)

The magnet used in this experiment produces a field with a force of 11.5 Tesla (T). The Earth’s magnetic field is equal to about 31 micro Teslas. The magnet holding your shopping list to your refrigerator is about .005 Tesla, the magnets in a loudspeaker are about 1 to 2 Teslas in strength, and the magnetic force of an MRI or similar device, for medical imaging, is usually about 3 Teslas or less. If you were to attach a magnet of 11.5 Teslas to your refrigerator, you would not be able to pry it off.

In this experiment, the magnet was used to “levitate” fruit flies for 22 days as they developed from embryos to larvae to pupae and eventually to adults. The flies were kept at a certain distance above the magnet where the net repulsive effect of the magnet on the water and other molecules was equal to and opposite of the effects of gravity. Other flies were placed below the magnet at the same distance, where they experienced the equivalent of double the Earth’s gravity.

The study examined how the expression of genes differed depending on the simulated gravitational field as well as in a strong magnetic field that did not simulate a change in gravity. Doubling the Earth’s gravity changed the expression of 44 genes, and canceling out gravity altered the expression of more than 200 genes. Just under 500 genes were affected by the magnetic field alone, with expression of the genes being either increased or decreased. The researchers were able to subtract the effects of magnetism from the effects of increased or decreased gravity and thus isolate which genes seemed to be most sensitive to changes in gravity alone. According to the researchers, “Both the magnetic field and altered gravity had an effect on gene regulation for the flies. The results of this can be seen in fly behaviour and in successful reproduction rates. The magnetic field alone was able to disrupt the number of adult flies from a batch of eggs by 60%. However the concerted effort of altered gravity and the magnet had a much more striking effect, reducing egg viability to less than 5%.”

The most affected genes were those involved in metabolism, the immune system’s response to fungi and bacteria, heat-response genes and cell signalling genes. This indicates that the effects of gravity on the developmental process in animals is profound.

The most important outcome of this research is probably the proof of concept: It demonstrates that this technique can be used to study the effects of low gravity on biological processes. We can expect more-refined results that inform us of specific processes that are altered by gravity, and possibly develop ways of offsetting those effects for humans or other organisms on long-distance space flight. Eventually, we may be able to send a fruit fly to Mars and return it safely.

Herranz, R., Larkin, O., Dijkstra, C., Hill, R., Anthony, P., Davey, M., Eaves, L., van Loon, J., Medina, F., & Marco, R. (2012). Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster BMC Genomics, 13 (1) DOI: 10.1186/1471-2164-13-52

Otavia is globular or ovoid in shape. Image is Figure 6 from the paper by Brain et al. and is provided under Creative Commons Copyright.

Life on Earth began very soon after the planet formed about 4.5 billion years ago. After the planet cooled enough, perhaps only tens of millions or a few hundred million years passed before the first life-like things existed. The geological record is sparse for that early period, about 3.5 billion to 3.8 billion years ago, so we can’t be sure. (And it may depend in part on how one defines “life.”) For the next few billion years, it seems, single-celled organisms had the run of the planet. Eventually, multi-celled organisms with differentiated tissue—like organs or other body parts—evolved from a subset of these single-celled forms. It is tempting to assume that the earliest multi-celled organisms were colonies of similar cells somehow functioning together (lots of life forms like this exist today), and that differentiation into different kinds of tissues evolved from this relationship, but the direct evidence to demonstrate this in the fossil record does not yet exist.

For years and years, the earliest evidence of early “metazoans” (animals with body parts) hovered around a half a billion years ago, but over time, earlier and earlier finds were made and the oldest date of something we would recognize as an animal was pushed back in time to about 650 million years ago. Now a new discovery pushes that date back.

A team of researchers based in Namibia, South Africa, Australia and the United Kingdom now report fossils from a Namibian deposit that seem to be animals and apparently date to about 760 million years ago. This extends the known time span of animals on the planet by about 17 percent.

The organisms are named Otavia antiqua and were like sponges. The genus name comes from the rock formation in which they were found, the Otavi Group, though they are also found elsewhere in Namibia. The rock formations in which they are found are several kilometers thick and were deposited in shallow marine environments on an ancient continental shelf. The deposits include volcanic rocks that are dated with a very accurate “parent-daughter” technique using uranium and lead. The dates are further verified by the stratigraphic location of the deposits beneath rocks dated to about 635 million years ago.

Otavia antiqua vary in size from less than half a millimeter to about 5 millimeters (about one hundredth of an inch to 2 tenths of an inch) and are globular or oval in shape. They have little holes on their surfaces, some of which lead to passageways to an internal cavity.

It appears that Otavia antiqua deposited a matrix of minerals between cells to develop a structure, and had a hollow area inside which has subsequently been filled with sediment in the fossils. Presumably, this small creature fed by passively capturing and processing microbes that passed through the holes and into the opening.

Based on the nature of the sediment inside and outside the fossils, the research team thinks that some of the fossils were redeposited from their original location while others are found today in situ, meaning that the fossil is found in the location in which it originally lived (and died).

There are several alternative explanations for these fossils: They could be some form of stromatolite (a bacterial biofilm), or a cluster of plankton-like organisms. However, the researchers make a good case that none of the alternative explanations are likely.

The most striking thing about Otavia antiqua might be the longevity of the life form. It is found throughout ancient sediments that span about 200 million years. If this in fact represents the range of time over which Otavia antiqua existed, without changing, then we should be impressed. This time period spans the hypothesized “Snowball Earth” period during which the entire planet became frozen, or nearly so, multiple times.

I recommend printing out the picture of Otavia antiqua and framing it. You can hang it on the wall and tell people it is your distant ancestor! (Though in all likelihood a cousin and not a grandparent.)

Brain, C., Prave, A., Hoffmann, K., Fallick, A., Botha, A., Herd, D., Sturrock, C., Young, I., Condon, D., & Allison, S. (2012). The first animals: ca. 760-million-year-old sponge-like fossils from Namibia South African Journal of Science, 108 (1/2) DOI: 10.4102/sajs.v108i1/2.658

The winged albatross. Image courtesy of Flickr user AntarcticBoy

Weather changes not just from season to season, but also from year to year. Where I live in Minnesota, we had only a few days of frost before the year’s end, and January, normally the coldest month of the year, was relatively balmy. But in another year we might have days on end of sub-zero weather during the winter. It is hard for a person to detect climate change at this scale, even though global temperature measurements clearly show that the planet has warmed.

But every now and then something comes along that demonstrates a longer term trend that we can see and measure more directly. For instance, the USDA recently released a new version of its “Plant Hardiness Zone Map.” If you are a gardener in the United States, you probably already know about this map; its zones are used to determine what kinds of plants can be grown outdoors in your area, the estimated dates of the last killing frost in the spring and the first killing frost in the fall. This is at least the second time in my memory that this map has been redrawn with all the zones moved to the north, reflecting a warming planet in a way that every gardener can observe and understand.

Not all global climate changes are simple warming, however. Global warming causes changes in ocean and atmospheric circulation as well. Westerly winds in the southern Pacific Ocean have shifted south towards the pole and have become more intense. A recent study in Science shows that the foraging patterns of breeding Wandering Albatross (Diomedea exulans) on the Crozet Islands has been changed by global warming in a way that seems to benefit them now, but that will likely harm them in the future.

Albatross are members of the bird order Procellariiformes, also known as the “tubenoses” because of the tube-like “nostrils” on their beaks. There are about 170 species of this kind of bird, including the petrels, shearwaters, storm petrels, diving petrels, and albatrosses. It is commonly said that the ocean is the last great frontier on earth, and this is probably true. It should not come as a surprise, then, that the Procellariiformes are among the “last great frontiers” of birding and bird research. Since the tubenoses spend almost all of their time at sea, they are hard to study. They come to land only to breed, and even then, usually on remote islands. They are so committed to being in the air over the ocean or floating on the surface of the sea that most members of this order are unable to walk at all. One group of tubenoses has the capacity to shoot a stream of noxious liquid (from its gut) at potential predators, which is an interesting adaptation to being unable to stand up and peck at intruders attempting to eat one’s egg or chick. (See this post for more information on tubenoses and a review of an excellent recent book on the tubenoses of North America.)

Life-long mated pairs of albatross settle in a nesting area during breeding season to lay and incubate eggs, hatch them and care for the young. The nesting sites are communal, so it is impossible for a pair of nesting birds to leave their egg or chick alone while they go out to find food—fellow albatross in the same colony view unguarded eggs or chicks as free snacks. The demand for food increases as the chick grows and requires more and more seafood every day, but the time available for foraging remains at 50 percent of normal because the two parents have to split the duty of guarding the nest and looking for food. In addition, dozens or perhaps hundreds of albatross from a given colony are foraging in the same general area, because they are all tending to nests at the same time. This probably diminishes the total amount of food that is available.

For all these reasons, foraging during nesting is a stress point in the life history of albatross. The birds forage by soaring around over the ocean, using wind as their main form of propulsion, literally sniffing out food sources (they have excellent smelling abilities). Therefore, the pattern of oceanic winds should matter a lot to their survival, especially during breeding season.

Which brings us back to changes in wind patterns due to global warming. The study by Henri Weimerskirch, Maite Louzao, Sophie de Grissac and Karine Delord is destined to become a classic because it touches on a sequence of logically connected observations to tell a compelling story. For my part, I’m going to use this in a classroom to demonstrate interesting science at my next opportunity. Let’s go over it step by step.

Albatross breeding is clearly difficult, and failure is likely common. One indicator of this is the fact that wandering albatross lay only one egg per season. Most coastal and terrestrial birds lay more than one, and in many species the number they lay varies from year to year depending on conditions. If wandering albatross lay only one egg, ever, there is a sort of underlying biological expectation of a low success rate.

For most birds, size matters. Within the normal range for a species, individual birds grow larger when conditions are good, and those birds do better in periods of difficulty because a large body stores more reserves and provides for more effective competition with other birds. A bird can grow large and bring lots of food back to the nest only if foraging is good, and the amount of food a bird obtains in a day is a combination of time (how long one forages) and the amount of food available in the environment.

The amount of food an albatross can obtain depends in part on the total area of the ocean that is searched each day, which in turn depends on how fast the bird flies. Since the albatross soars on the wind most of the time, this means that everything depends on factors such as the speed and direction of the wind. The study we are looking at today combines all of these things in an elegant exposé of the link between climate and the difficult job of producing baby albatrosses.

The wandering albatross travel enormous distances from their breeding grounds, often going more than 1,000 miles before returning to the nest to relieve their mate from guard duty. Males forage more widely and more to the south than females, who prefer northern waters. During this time, the birds use the wind as their primary form of locomotion. The researchers have shown that the winds in this region have increased in strength by a measurable amount, owing to shifts related to global warming. The average wind speed has gone up by about 10 percent from the 1990s to the present day. This allows the birds to move from foraging area to foraging area more swiftly than otherwise possible.

The total amount of time it takes both male and female albatross to complete a full journey of a given distance has decreased by between 20 percent and 40 percent from the 1990s to the present, and the speed at which the birds are observed to fly has gone up about the same for females, though the observed speed increase for males is not statistically significant. This is direct evidence that the amount of time spent foraging is less under present conditions than it was in the recent past, and it can be inferred that this is caused by the correlated increases in wind speed.

During the same period of time, the birds have gotten bigger. In 1990 the average female was about 7,500 grams and by 2010 females were about 8,500 grams. Males increased by about the same percentage, going from the mid-9,000 range to about 10,500 grams. These differences in mass are not reflected in the overall dimensions of the bird, just their weight. This indicates that during periods when the birds are on average smaller, many are underfed.

Breeding success for albatross varies considerably. The chance of successfully launching a baby albatross from the nest for the 350 pairs studied ranges from about 50 percent to just over 80 percent depending on the year (I’m leaving out one really bad year when the success rate was only 25 percent). During the past 40 years, over which it is thought the wind patterns have changed as described above, the “moving average” of breeding success (taking a few years together into account to dampen natural variation) has changed from about 65 percent to about 75 percent. These birds indeed seem to be benefiting from changes in wind pattern caused by global warming.

Most changes in weather, patterns of wind and rain and other effects of global warming are negative, as any review of the literature on this topic over the past decade will show. The benefits being experienced by these birds is unusual. But it may also be temporary. The researchers who produced this result say that the shift of winds towards the poles that brought higher energy patterns to these islands is likely to continue. As wind speeds increase, the benefit the birds will receive will at first level off then start to decrease, as overly windy conditions are bad for the albatross. The shift of westerly winds to the south of the islands will probably decrease the viability of foraging over the next few decades because it will make it easier for the birds to get to places with lower quality forage and thus decrease the rate of obtaining food. So, if the current changes in wind patterns are a gravy train for the Crozet Island wandering albatross, the train may eventually leave the station without them.

Weimerskirch, H., Louzao, M., de Grissac, S., & Delord, K. (2012). Changes in Wind Pattern Alter Albatross Distribution and Life-History Traits Science, 335 (6065), 211-214 DOI: 10.1126/science.1210270

The Caldera of Santorini is today a ring of islands in the Aegean. Photograph by Flickr member EmreKanik.

A caldera is a very large crater that forms after a very large volcanic eruption. The eruption is explosive and ejects a lot of material. Most of what comes out of the volcano is blown a great distance into the atmosphere and over a large area, so a huge volume of the local landscape is simply gone—thus the large crater.

Many people know about the Yellowstone Caldera because it is the location of a lot of interesting ongoing thermal and volcanic activity, some of which has been in the news lately, and it has even been featured in a recent epic disaster fiction film called 2012 in which the re-explosion of the Yellowstone Caldera is only one problem of many faced by the film’s heroes and heroines.

Somewhat less known but still famous is the Santorini Caldera. It is in the Aegean Sea, in Greece, near the island of Crete. Santorini blew about 1,600 B.C. and seems to have caused the end of the Minoan Civilization; the edge of the volcano’s caldera is now a ring of islands. By comparison with Yellowstone, Santorini is small. The Yellowstone Caldera is about 55 by 72 kilometers in size, while Santorini’s is about 7 by 12 kilometers.

Santorini is the subject of an investigation just reported in the journal Nature. The volcano has blown numerous times in the past. The investigation shows that the last explosion, the one at about 1,600 B.C., was preceded by a stunningly short period of build-up of underground magma. It seems as though the magma, enough for a very large eruption, moved into the zone beneath the caldera in two or more events less than 100 years prior to the explosion, with a significant amount of the magma moving into place just a few years before the blast.

If we go back a decade or so, volcanologists thought that the buildup to a major eruption like this would take more time, perhaps many centuries. Various lines of evidence have caused scientists to start to think that the buildup to blast-time might be shorter than that, and the present report is an excellent direct measurement of the timing which seems to confirm these growing suspicions.

How can scientists tell that it happened this way? Using volcano forensics, of course! Here’s the basic idea:

When shocking events happen, such as the intrusion of a bunch of magma into an area of rock, or associated seismic activities, the various chemicals in magma become “zoned.” Waves of energy passing through the molten rock cause bands of specific types of chemicals to form. During a period of no shocks, if the temperature is high enough, these bands dissipate. Some bands dissipate in very short periods of time, others over very long periods of time. If at any point the magma is released in a volcanic explosion such as the type that forms a caldera, the material suddenly cools and the state of the bands, dissipated to a certain degree, is preserved. Later, sometimes thousands of years later, geologists can study the rocks and estimate the amount of time between shock event and the volcanic explosion by measuring how much dissipation has occurred. It is a sort of magma-based clock.

In the case of Santorini, everything seems to have happened well within a century. This formation of a magma chamber large enough to cause a major eruption occurred after an 18,000-year-long dormant period. So, if we were thinking that the long period of time between caldera eruptions was characterized by a slow and steady buildup of magma, we were probably wrong. The real significance of this is that we can’t look at a caldera that is known to have erupted multiple times and rule out a future eruption simply on the basis of a low level of current activity. And of course, we are left wondering what initiates this rather rapid recharge of the magma underneath a caldera.

It’s a good thing that scientists are studying and monitoring these volcanoes!

Druitt, T., Costa, F., Deloule, E., Dungan, M., & Scaillet, B. (2012). Decadal to monthly timescales of magma transfer and reservoir growth at a caldera volcano Nature, 482 (7383), 77-80 DOI: 10.1038/nature10706