Thursday, October 15, 2009
A Duke University study has found that the absence of the appetite hormone leptin can determine whether obese mice experience arthritis, no matter how heavy they are.
"We were completely surprised to find that mice that became extremely obese had no arthritis if their bodies didn't have leptin," said Farshid Guilak, PhD, director of orthopaedic research in the Duke Department of Surgery.
"Although there was some earlier evidence that leptin might be involved in the arthritis disease process, we didn't think that there would be no arthritis at all."
In fact, the joints from the obese mice in the study appearing in the journal Arthritis & Rheumatism looked better than those of the normal control mice, Guilak said. "However, in another study, we found that mice that gained half as much weight on a high-fat diet but processed leptin normally showed significant knee osteoarthritis."
Leptin influences many of the factors involved in osteoarthritis -- body weight, inflammation, sex hormone levels, and bone metabolism, said lead author Tim Griffin, PhD, who was at Duke Orthopaedic Department and now is an assistant member of the Free Radical Biology and Aging Program at the Oklahoma Medical Research Foundation.
"That also makes leptin challenging to study, however, because it's difficult to isolate which pathway is being altered to prevent the development of osteoarthritis."
Leptin is a well-known regulator of appetite, but this is the first time scientists have reported a role for leptin as a metabolic link between obesity and altered cartilage metabolism in joints.
The role of obesity as a risk factor for arthritis is well characterized, but it was thought to be merely a case of overloading joints with extra weight.
"It hadn't been studied beyond that," Guilak said. "We knew from other studies that obese people got arthritis in their hands, too, which don't bear weight. This indicated that something besides just body-weight level affected their joints."
The Duke team set out to learn whether the increased body fat of obesity causes an inflammatory response in joints -- an imbalance of the immune system signaling proteins called cytokines and other chemicals in osteoarthritis.
They studied mice that were leptin-deficient or deficient in leptin receptors -- mice that didn't have any effective leptin in their bodies. Both types of mice overate and gained weight.
Then they compared the study mice with normal mice to document knee osteoarthritis. The measurements included pro- and anti-inflammatory cytokines present in arthritis, and several tests to assess bone changes in the knees of the mice.
The knee bones of the leptin-free, obese mice did change, but without forming osteoarthritis. The levels of inflammatory cytokines, which correlate with arthritis, were largely unchanged in these mice. The results suggested that leptin may have a dual role in the development of osteoarthritis by regulating both the skeletal and immune systems.
What does this mean for people? "Obesity is still the number one preventable risk factor of osteoarthritis, but now it seems body fat by itself is not what is causing it," Guilak said.
"If you are obese, there are benefits to losing weight in terms of arthritis. For example, if you are obese and lose just 10 pounds, pain decreases significantly. Pain modulation is another clue it might be a chemical or systemic metabolic effect, rather than just a mechanical effect of less weight on the joints."
As with many studies that yield unanticipated findings, "we have a lot of additional questions and experiments that need to be done to further understand how leptin mediates the development of osteoarthritis," Griffin said.
"With obesity and osteoarthritis, there are good similarities between humans and mice," Guilak said. "If we can find a pathway that links a high-fat diet with arthritis, then we can try to identify and block the inflammatory mediators that are linked with the dietary fat."
Cells in a developing animal require information about their position with respect to other cells so that they can adopt specific patterns of gene expression and function correctly. The most accepted paradigm is that this positional information comes in the form of chemical signals called morphogens; morphogens are differentially distributed across the developing field, with cells acquiring the information about their position relative to their neighbors by "measuring" and interpreting the local concentrations of the morphogen.
Despite the identification of several families of morphogens in many organisms, the hypothesis that cells differentially respond to morphogen concentrations generally hasn't been directly tested.
The Caltech researchers, led by assistant professor of biology Angelike Stathopoulos, used an approach that combines mathematical modeling and developmental genetics experiments to examine the mechanisms underlying patterning of the developing wing in the fruit fly, Drosophila melanogaster. They found that cells cannot adopt multiple patterns of gene expression solely by measuring the local concentration of a morphogen.
"During metamorphosis, imaginal disc tissues need to form structures that contribute to the adult body plan," explains Stathopoulos. Imaginal discs are parts of the insect larva that will become structures that contribute to the adult body plan. "This imaginal disc tissue is plastic, in that the cells are still making decisions about what part of the organ they should develop into. A decision has been made that these cells must make 'body part X,' but how do they determine whether to make the proximal or distal portion, or decide which is facing up or down? This is where morphogens come in."
In fruit flies, a regulatory molecule called Hedgehog provides such information, along the anterior-posterior axis (from base to tip) of the developing wing. For the wing to properly form, cells along this axis need to "act" by turning on the Hedgehog signaling pathway, although not all of the cells do so, Stathopoulos says.
"We found that in the developing wing of the fruit fly, cells do not acquire positional information by only measuring the concentration of the Hedgehog morphogen at a given time, but instead require information about their history of exposure," says Marcos Nahmad, a graduate student in control and dynamical systems at Caltech, jointly supervised by Stathopoulos and John Doyle, the John G. Braun Professor of Control and Dynamical Systems, Electrical Engineering, and Bioengineering. Nahmad is the first author of a paper about the research, coauthored by Stathopoulos, that appears in the September 29 issue of the open-access online journal PLoS Biology.
In their experiments, the researchers found evidence that certain cells receive the Hedgehog signal only for a short period of time, and this transient exposure causes them to adopt a gene expression pattern that is different from that of other cells that receive the Hedgehog signal constantly, and from those that never received it at all.
In a sense, says Stathopoulos, the cells are able to "remember" that they've been exposed to the morphogen. "What I mean is they remember having 'seen' a morphogen concentration that activates a signal within them. Even if the concentration of the morphogen decreases subsequently, cells still retain the ability to activate the pathway."
"An exciting outcome of our model is that the ability of cells to respond to the history of morphogen exposure is wired in the gene network architecture that controls patterning of the developing wing. As the Hedgehog pathway architecture is widely conserved from flies to humans, this mechanism of patterning may explain how cells in other developing systems acquire positional information," Nahmad says.
"As developmental biologists, we want to understand how the body plan is specified, and how different animals exhibit different shapes and patterns. What we've shown here is that it's important to consider the temporal sequences of events," Stathopoulos says.
"The dynamics of the system are instructional. In the past, for the most part, this has been ignored, because it's just too complicated. People have formulated models by looking at the endpoint. We believe that even more insights into patterning have likely been missed for this reason," she adds.
California Institute of Technology (Caltech)
Captive pairs of spotted hyenas (Crocuta crocuta) that needed to tug two ropes in unison to earn a food reward cooperated successfully and learned the maneuvers quickly with no training. Experienced hyenas even helped inexperienced partners do the trick.
When confronted with a similar task, chimpanzees and other primates often require extensive training and cooperation between individuals may not be easy, said Christine Drea, an evolutionary anthropologist at Duke University.
Drea’s research, published online in the October issue of Animal Behavior, shows that social carnivores like spotted hyenas that hunt in packs may be good models for investigating cooperative problem solving and the evolution of social intelligence. She performed these experiments in the mid-1990s but struggled to find a journal that was interested in non-primate social cognition.
“No one wanted anything but primate cognition studies back then,” Drea said. “But what this study shows is that spotted hyenas are more adept at these sorts of cooperation and problem-solving studies in the lab than chimps are. There is a natural parallel of working together for food in the laboratory and group hunting in the wild.”
Drea and co-author Allisa N. Carter of the Univ. of California at Berkeley, designed a series of food-reward tasks that modeled group hunting strategies in order to single out the cognitive aspects of cooperative problem solving. They selected spotted hyenas to see whether a species’ performance in the tests might be linked to their feeding ecology in the wild.
Spotted hyena pairs at the Field Station for the Study of Behavior, Ecology and Reproduction in Berkeley, Calif. were brought into a large pen where they were confronted with a choice between two identical platforms 10 feet above the ground. Two ropes dangled from each platform. When both ropes on a platform were pulled down hard in unison -- a similar action to bringing down large prey -- a trap door opened and spilled bone chips and a sticky meatball. The double-rope design prevented a hyena from solving the task alone, and the choice between two platforms ensured that a pair would not solve either task by chance.
The first experiment sought to determine if three pairs of captive hyenas could solve the task without training. “The first pair walked in to the pen and figured it out in less than two minutes,” Drea said. “My jaw literally dropped.”
Drea and Carter studied the actions of 13 combinations of hyena pairs and found that they synchronized their timing on the ropes, revealing that the animals understood the ropes must be tugged in unison. They also showed that they understood both ropes had to be on the same platform. After an animal was experienced, the number of times it pulled on a rope without its partner present dropped sharply, indicating the animal understood its partner’s role.
“One thing that was different about the captive hyena’s behavior was that these problems were solved largely in silence,” Drea said. Their non-verbal communication included matching gazes and following one another. “In the wild, they use a vocalization called a whoop when they are hunting together.”
In the second and third experiments, Drea found that social factors affected the hyenas’ performance in both positive and negative ways. When an audience of extra hyenas was present, experienced animals solved the task faster. But when dominant animals were paired, they performed poorly, even if they had been successful in previous trials with a subordinate partner.
“When the dominant females were paired, they didn’t play nicely together,” Drea said. “Their aggression toward each other led to a failure to cooperate.”
When a naïve animal unfamiliar with the feeding platforms was paired with a dominant, experienced animal, the dominant animals switched social roles and submissively followed the lower-ranking, naïve animal. Once the naïve animal became experienced, they switched back.
Both the audience and the role-switching trials revealed that spotted hyenas self-adjust their behavior based upon social context.
It was not a big surprise that the animals were strongly inclined to help each other obtain food, said Kay Holekamp, a professor of zoology at Michigan State University who studies the behavioral ecology of spotted hyenas.
“But I did find it somewhat surprising that the hyenas’ performance was socially modulated by both party size and pair membership,” Holekamp said. “And I found it particularly intriguing that the animals were sensitive to the naïveté of their potential collaborators.”
Researchers have focused on primates for decades with an assumption that higher cognitive functioning in large-brained animals should enable organized teamwork. But Drea’s study demonstrates that social carnivores, including dogs, may be very good at cooperative problem solving, even though their brains are comparatively smaller.
"I'm not saying that spotted hyenas are smarter than chimps,” Drea said. “I’m saying that these experiments show that they are more hard-wired for social cooperation than chimpanzees.”
(Photo: Christine Drea)
There is growing evidence that animals may share humans’ ability to reflect upon, monitor and regulate their states of mind, according to a study published in Trends in Cognitive Sciences this month. Dr David Smith, comparative psychologist at the University of Buffalo, makes this conclusion in a review of the new and rapidly developing area of studying animal metacognition. He was supported by the European Science Foundation EUROCORES programme ‘Consciousness in a natural and cultural context’ (CNCC).
Humans can feel uncertainty. You know if you do not know or remember – a perfect example of this is the feeling of something being on the tip of your tongue. This capacity to be aware of our own thinking is known as metacognition. Establishing whether non-human animals also share this sophisticated human capacity is important for understanding their consciousness and self-awareness. The study of metacognition is based on the idea that human minds in particular have a function that monitors or controls perception and memory.
“It is a crucial goal of comparative psychology to establish firmly whether animals share humans’ capacity to think about thinking,” says Dr David Smith. “Metacognition rivals language and tool use in its potential to establish important similarities or differences between human and animal minds.”
To find out whether non-human animals do have knowledge of their own cognitive states researchers have studied a dolphin, pigeons, rats, monkeys and apes using tests involving perception, memory and food-concealment. The results offer growing evidence that some animals do indeed have functional equivalents to humans’ consciousness and to humans’ cognitive self-awareness.
Among these species are dolphins and macaque monkeys (an Old World monkey species). Smith recounts the original animal-metacognition experiment with Natua the dolphin: “When uncertain, the dolphin clearly hesitated and wavered between his two possible responses. But when certain, he swam toward his chosen response so fast that his bow wave would soak the researchers’ electronic switches. Practicing safe science, the researchers were reduced to buying condoms to protect the apparatus from the exuberantly confident dolphin.”
In sharp contrast, other animals do not have the same capacity. Pigeons in several studies have so far not expressed any capacity for metacognition and several converging studies now show that capuchin monkeys (a New World monkey species) only express a limited capacity for metacognition. This raises important questions about the evolution of the reflective mind in primates and opens a new window on reflective mind in animals overall, illuminating its evolutionary emergence and allowing researchers to trace the precursors to human consciousness.
Comparative psychologists are cautious about labeling animals’ functional parallels with humans as a definite indicator of consciousness. Yet the fact that some animals’ flexibly use metacognition without training means it is likely to reflect their conscious awareness.
Smith is recognized for his research in the field of animal cognition. He and his colleagues pioneered the study of metacognition in nonhuman animals, and they have contributed some of the principal results in this area, including many results that involve the participation of Old World and New World monkeys who have been trained to use joysticks to participate in computer tasks. Smith is one of a growing number of American participants in EUROCORES, through support from the USA’s National Science Foundation. The metacognition project is led by professor Joëlle Proust from the Institut Jean-Nicod in Paris, France. Dr Smith collaborates with partners from Austria, France, Germany and the UK to develop comparative knowledge of metacognitive processes, by exploring how similar these capacities are in non-human animals, human children and human adults.
Dr Eva Hoogland, EUROCORES coordinator for the cognitive sciences at the European Science Foundation, comments: “The metacognition project is an exciting example of an international, interdisciplinary environment that is carefully prepared and managed, where partners from disciplines as diverse as developmental psychology, comparative biology and philosophy respect each other’s work. This study shows how this has resulted in opening up promising research avenues to answer some of the most important research questions that currently face us.”
European Science Foundation
That's the question Purdue University researchers are investigating as they start a new study aimed at measuring greenhouse gases from dairy cows. Albert Heber, principal investigator and a professor of agricultural and biological engineering, said the study is part of an industry-wide effort to reduce greenhouse gas emissions related to fluid milk.
"The dairy industry understands that in order to adopt best practices that will help lower greenhouse gas emissions in the dairy supply chain, it must first know where the mitigation opportunities exist," Heber said.
The study is being funded by the Innovation Center for U.S. Dairy and is one of several studies that will be used to measure the entire carbon footprint of fluid milk - from the farm to the glass. Researchers from the University of California Davis, Cornell University, the University of Minnesota and Washington State University are collaborating on the project.
"Measuring the greenhouse gas emissions of dairy cows will help determine the extent to which the dairy industry contributes to U.S. greenhouse gas emissions," said Rick Naczi, the group's executive vice president of strategic industry analysis and evaluation. "Preliminary scan level research was conducted last year that showed the dairy industry accounts for less than 2 percent of total U.S. greenhouse gas emissions. Now, we are expanding our efforts by partnering with respected academic institutions like Purdue and engaging in extensive research to assure that our efforts are based on sound science as we address the environmental, economic and social importance of reducing our carbon footprint."
Carbon dioxide, methane and nitrous oxide will be monitored at five barn sites and two manure lagoons in Indiana, Wisconsin, California, Washington and New York. Mobile laboratories set up for the National Air Emissions Monitoring Study, of which Heber also is principal investigator, are being used to take the measurements in this study as well.
"We began collecting some greenhouse-gas data as early as 2007, but now we have all the equipment we need and we've been getting data on all parameters of it for about a month," said Bill Bogan, operations manager for the two studies.
Tubes will draw air from each of several exhaust fans and background locations. The air will be fed into a series of analyzers that measure the concentrations of the gases. Those concentrations can be used to determine the amount of each gas emitted for a particular time period and per animal. Data will be updated every minute.
Heber said the gas comes from both the cow and the manure. Manure gas is easiest to address. Different manure management practices may increase or decrease total emissions, he said.
"The type of storage and handling procedures may contribute to how much gas is escaping from the manure," Heber said.
Most of the previous studies on dairy greenhouse gas emissions were done in Europe and Canada and don't reflect U.S. climate and management practices. This study will provide country- and region-specific greenhouse-gas emission rates from U.S. dairy operations, which can be used by the Intergovernmental Panel on Climate Change for modeling emissions.
The significance of vegetation for slowing erosion and reinforcing banks has been known for a long time, but this is the first time it has been scientifically demonstrated as a critical component in meandering. Sand is an ingredient generally avoided in stream restoration as it is known to disrupt salmon spawning. However, Braudrick and his colleagues have shown that it is indispensable for helping to build point bars and to block off cut-off channels and chutes--tributaries that might start and detract from the flow and health of the stream.
The model is a first for the delicate balance of ingredients of the model flood plain, gravel (sand), fine sediment, vegetation and water to come together in such a way that the stream took life and behaved in the way its healthy counterparts in nature would at 50 to 100 times the size and on the scale of hours instead of years.
In 130 hours after being set into motion, this train-set size (6m x 17m) river eroded its banks and built point bars by depositing model sand and gravel moving around in its environment the way parts of the Mississippi River would over five or seven years.
In nature, this behavior not only achieves a "picture perfect" waterway with pleasing bends, but it yields what earth scientist Braudrick calls "more biological bang for the buck."
"Meandering" generally occurs in streams with moderate slopes and is a common form of river between canyon-bound rivers in the mountains and deltas near the ocean. The physics and geology of meandering streams combine to yield both shallow portions as well as deeper pools. The diversity of habitat is a more hospitable environment to sustain a higher diversity of species. This is in contrast to another stream type with many islands but more uniform and shallower water called "braided streams."
Stream restoration is an extremely complex and delicate science. Because there is no formula to create meandering streams. Successful stream restorers almost require a sixth sense to get everything right and set a sustainable environment into motion, and not every restored stream lasts. Some form extra channels becoming braided streams; some stagnate.
Braudrick and his colleagues hope to shed light on the necessary conditions for sustained meandering in coarse bedded rivers. They have used a clever combination of painted sand that stands in for gravel, a light weight plastic that looks like sugar for sand, and alfalfa sprouts that stand in for the deep rooted vegetation, such as cottonwoods or willows that grow along many meandering rivers in the wild.
(Photo: Zina Deretsky, National Science Foundation)
National Science Foundation
In the search for better ways to fly, researchers have long pondered the question: Which is a better system -- the flapping wings of birds and insects, or the fixed wings of your average 747?
The answer depends on a host of variables, including the size of the object and the type of flight. If maneuverability is the goal, birds and insects seem to have the advantage. When it comes to efficiency, most aeronautical engineers would agree that the fixed-wing airplane is the smartest design.
But according to a new Cornell study, an optimized flapping wing could actually require 27 percent less power than its optimal steady-flight counterpart at small scales.
The study, by Jane Wang, professor of theoretical and applied mechanics, and graduate student Umberto Pesavento, is published in the Sept. 11 issue of Physical Review Letters (103:11).
To find an optimum combination of motion and wing orientation, the researchers analyzed the interactions between a wing and its aerodynamic wake in two dimensions for a group of flapping motions with characteristics similar to those observed in hovering insects, using fruit fly wing dimensions as a model.
Doing such calculations for systems in three dimensions would require many dozens of hours per trial on most computers, which would make it impossible to find an optimum among infinite possibilities, Wang said.
"We wanted to include as much as possible so we don't miss the good solutions, but we can't include everything because it would be impossible," Wang said.
For the fixed-wing scenario, the optimum occurs at a specific angle of attack. Therefore, at first glance, flapping flight would seem less efficient because the wing would necessarily deviate from the optimum condition.
Building on Wang's previous work studying insect flight, the researchers constructed a special family of wing motions that allowed them to optimize a range of parameters, including optimum angle of attack, turning speed, frequency and timing between pitching and flapping for a wing of the same size and with the same amount of weight to support.
The most efficient flapping motion, they found, required significantly less power than the corresponding fixed-wing motion. Unlike a simple sinusoidal, or symmetrical up-and-down flapping motion, which is more commonly studied but much less efficient, the optimized motion holds the wing's angle of attack steady for a longer time near the optimum angle for its fixed counterpart; and also takes advantage of air patterns created as it reverses direction.
The discovery of one instance in which flapping is more efficient than steady flight, Wang said, shows that our intuition about flight efficiency isn't always right, especially when unsteady aerodynamics is at play.
At a more practical level, the study shows the possibility of substantially improving design of flapping flight, which typically has low efficiency, using a trial-and-error approach. "The trial-and-error approach is particularly ineffective for these problems, where poor solutions dominate the landscape and good solutions are few," Wang said.
(Photo: Cornell U.)
Space environments can deliver a beating to spacecraft electronics. For decades, satellites and other spacecraft have used bulky and expensive shielding to protect vital microelectronics—microprocessors and other integrated circuits—from space radiation.
Researchers at the Georgia Institute of Technology are developing ways to harden the microchips themselves against damage from various types of cosmic radiation. With funding from NASA and other sponsors, a Georgia Tech team is investigating the use of silicon-germanium (SiGe) to create microelectronic devices that are intrinsically resistant to space-particle bombardment.
Key to the investigation is determining exactly what happens inside a device at the instant a particle hits, says principal investigator John D. Cressler, who is a Ken Byers Professor in the Georgia Tech School of Electrical and Computer Engineering.
“Cosmic radiation can go right through the spacecraft, and right through electronics on the way, generating charge inside the device that can cause electronic systems to produce errors or even die,” Cressler said. “There’s a lot of interest in improved hardening capabilities from NASA, the Department of Defense and communications companies, because anything that flies into space has to withstand the effects of this radiation.”
Silicon-germanium holds major promise for this application, he adds. SiGe alloys combine silicon, the most common microchip material, with germanium, at nanoscale dimensions. The result is a material that offers important gains in toughness, speed and flexibility.
Any space vehicle, from NASA spacecraft and military vehicles to communications and global positioning system (GPS) satellites, must contend with two principal types of cosmic radiation.
—Ionizing radiation includes ubiquitous particles such as electrons and protons that are relatively high in energy but not deeply penetrating. A moderate amount of metal shielding can reduce their destructive effect, but such protection increases a space vehicle’s launch weight.
—Galactic cosmic rays include heavy ions and other extremely high-energy particles. It is virtually impossible to protect against these dangers.
Faced with damaging radiation, engineers have for decades augmented shielding with a circuit-design technique called “triple modular redundancy.” This approach utilizes three copies of each circuit, all tied into logic circuitry at one end. If one copy of the circuit is corrupted by cosmic radiation and begins producing bad data, the logic circuit opts for the matching data produced by the other two circuits.
“The problem with this approach is that it requires three times the overhead in power, real-estate and cost,” Cressler said.
Other traditional circuit-protecting techniques have included the hardening-by-process method. In this approach, integrated circuits are produced using special processes that harden the chips against radiation damage. The problem is this processing generally increases chip costs by 10 to 50 times.
As a result, the space community is eager to find ways to produce space-hardened microelectronic devices using only everyday commercial chip-making technologies, Cressler says. The savings in cost, size and weight could be very significant.
Silicon-germanium is a top candidate for this application because it has intrinsic immunity to many types of radiation. The catch is that, like other materials, SiGe cannot stand up to the extremely destructive heavy ions present in galactic cosmic rays.
At least, not yet.
Cressler’s team is analyzing exactly what happens inside a SiGe device when it’s subjected to the type of energy found in heavy ions. Using sophisticated new equipment, including an extremely high-speed oscilloscope, researchers can capture details of particle-strike events that last only trillionths of a second (picoseconds).
Working with NASA and the U.S. Naval Research Laboratory, Cressler is using an ultrafast laser to inject current into a silicon-germanium transistor. The aim is to emulate the effect of a heavy-ion strike in space.
“When I shine a laser on the device, it generates a pulse of current that may only last for a few picoseconds,” Cressler said. “Capturing the dynamics of that process—what it looks like in time and in its magnitudes—is important and challenging.”
Cressler’s investigation also involves firing actual ions at SiGe circuits. Using a focused ion microbeam at the Sandia National Laboratories, the Georgia Tech team can aim a single heavy ion at a given point on a device and capture those results as well.
The ultimate aim is to alter silicon-germanium devices and circuits in ways that will make them highly resistant to nearly all cosmic radiation, including heavy ions, without adding overhead.
Observing actual particle impacts in real time is key, Cressler says. Detailed computer 3-D models of particle strikes on SiGe devices and circuits—created with sophisticated numerical simulation techniques—have already been developed. But until researchers can compare these models to actual observed data, they can’t be sure the models are correct.
“If we get good fidelity between the two,” he added, “then we've know we have a good understanding of the physics.”
Step two, he adds, will involve using that information to design devices and circuits that are highly immune to radiation.
“One of the holy grails in this field is getting sufficient radiation hardness without resorting to any of the high overhead schemes such as shielding, process hardening, or triple modular redundancy,” he said. “And, in fact, we are closing in on that goal, using SiGe electronics.”
Blood doping or boosting the number of oxygen-carrying hemoglobin in red blood cells is one way humans have tried to acclimate to high elevation and enhance athletic performance. But there are risks involved. There is an upper limit to the number of blood cells that can circulate in the blood, and packing in extra increases the load on the heart and the circulatory system. Species native to high elevation regions don't typically have noticeably higher red blood cell counts.
A potentially better way to cope with low atmospheric pressure at high-altitude is to enhance the ability of hemoglobin to bind oxygen.
Following a trip to Argentina in 2001, McCracken began to ponder whether the differences he observed between populations of ducks that lived in the high Andes, above 3,000 meters (ca. 10,000 feet), were also evident in their hemoglobin genes.
The high plateau of Andes is a cold, dry, oxygen-depleted region. McCracken predicted that the ducks that resided here year-round likely experienced strong natural selection and that their hemoglobin genes would differ from closely related populations in the lowlands.
Each year from 2001 to 2005, McCracken or members of his research team returned to South America to sample five pairs of dabbling duck populations in both the lowlands and the highlands and compare their hemoglobin genes using DNA sequencing. The ducks were collected from the far north of Peru, through Bolivia and Argentina, south to the Strait of Magellan and the Falkland Islands, a 6,000 kilometer (3,700 mile) transect which spans approximately a 5,000 meter (16,400 feet) change in elevation.
In the highland duck populations, McCracken and his colleagues found, on average, three amino acid substitutions (as few as one but never more than five) in the two genes that code for the major hemoglobin protein. The same substitutions were either absent or very rare in lowland populations of the same species. The hemoglobins also differed from other genes in that they showed a much stronger pattern of genetic differentiation.
That few genetic changes might have resulted in adaptation to high altitude is not surprising, McCracken says, as one or two substitutions can have large measureable effects on a protein like hemoglobin. The selection pressure, or intensity with which an environment weeds out unfit organisms, is strong and well defined in this case and such changes could come about relatively rapidly over few generations.
"We still haven't answered the question of whether these mutations increase hemoglobin-oxygen affinity," McCracken said. "An additional series of studies will be required to determine how each substitution that was observed influences blood-oxygen and hemoglobin-oxygen affinity."
University of Alaska Fairbanks