Volume 6, Issue 47 October 2009
Old Bones Hold the Secret to Strong Skeletons
Sabrina Agarwal travels the world studying ancient skeletons for clues to preventing osteoporosis, often bringing samples back to study in the Skeletal Biology Lab in the Department of Anthropology. Image credit: courtesy Sabrina Agarwal
Among seniors, the brittle bones of osteoporosis are now nearly as ubiquitous as gray hair and bifocals. American women in particular now face a 1 in 2 chance of fracturing their bones after age 50. Those fracture rates are among the highest in the world despite all of the milk, cheese and calcium supplements we ingest.
But fragile bones, argues Berkeley professor of anthropology Sabrina Agarwal, are a relatively recent phenomenon. "Modern women shouldn't think of osteoporosis as something that's inevitable, that's just part of being a woman growing old and a consequence of menopause," she says.
A biological anthropologist, Agarwal studies skeletons from earlier human populations as well as modern primates to understand how bones age. What she finds is that fragility fractures, such as those of the hip and wrist so characteristic of seniors with osteoporosis, were almost unheard of in earlier times.
"Populations in the past had very different lifestyles and did very different things. That makes them ideal for seeing what bone loss, maintenance and growth look like under different circumstances," Agarwal says. Pinpointing those differences, she hopes, may lead to better advice on how to prevent and treat osteoporosis today.
Human bone undergoes changes in strength and structure with age. This is due both to changes in bone density but also internal structure. From top: Fourth lumbar vertebrae from a juvenile; adult; and an older adult from the Neolithic community of Çatalhöyük, Turkey. Image credit: Courtesy Sabrina Agarwal, in Agarwal and Glencross (in press), "Bone Loss and Fragility Through the Lifecycle: A Paleopathological Perspective." In: Moffat, T, and Prowse, T (eds). Biosocial Perspectives on Human Diet and Nutrition. Berghahn Press (Oxford, New York)
One of the populations Agarwal has studied is from the medieval town of Wharram-Percy, in northern England. These rural peasant women, Agarwal has found, lose bone very differently than their modern industrialized counterparts. Instead of losing a dramatic amount of bone immediately after menopause, Wharram-Percy's women lost it gradually during their reproductive years. Further, those women who attained the age of 50 or older had little or no fragility-related fractures and possessed just as much bone as the village men. This is dramatically different from patterns of bone loss and osteoporosis seen in modern Western women.
By comparison, the medieval urbanites Agarwal has studied fall somewhere in between. Like modern Americans, women, buried in the Royal Mint cemetery near the Tower of London, lost the most bone after menopause, but still suffered few fragility-related fractures in old age.
Agarwal points to several factors that probably helped keep medieval women's skeletons strong throughout life. One is hard physical labor. Wharram-Percy women toiled in the fields for many hours a day as well as maintained a household in a time before running water and electricity. Many studies have shown that bones respond to biomechanical stress by becoming stronger.
Another factor is childbearing. In medieval times, women were generally either pregnant or nursing during the decades between 20 and 45. Most had four to five children over their lifetimes, and breast fed them for several years rather than just a few months. Medieval women also reached menarche several years later and menopause several years earlier than women today. As a result, they would have experienced about 40 periods throughout their lives compared to the current average of 210.
"It's a huge hormonal difference," Agarwal says. "Hormones affect breast cancer, the function of the ovaries, and heart risk. Yet no one has investigated the effect of this dramatically different hormonal milieu on bone."
The differences between urban and rural populations, she says, might be a combination of sunshine and female hormones. Rural women were more likely to work outdoors in the fields, where they could absorb more of the sunlight required to make the Vitamin D needed for strong bones. And urban women might have nursed their babies for slightly shorter periods of time.
The skeletons of a child and adult buried in the medieval-era churchyard at Wharram Percy, England. Image credit: Sabrina Agarwal, Mays (1998) The Archaeology of Human Bones, Routledge, London
Bone health, Agarwal concludes, is "very dependent on what environment you're living in and what lifestyle you're following."
Quality as well as quantity appears to affect bone strength. While modern medicine is primarily concerned with bone quantity, particularly bone mineral density, the organization and material properties of bone may influence bone fragility even more. The bones of the hip and spine have interiors that resemble a porous honeycomb. Such trabecular bone is a primary source of the bone mineral lost during osteopenia and its more advanced state, osteoporosis. How the body remodels the internal rod and stick structure that remains, Agarwal suspects, affects its structural soundness.
"If it's reorganized poorly, you can have a higher risk of fracture. As you absorb bone in your spine, you might lose more of the horizontal pieces, but the vertical ones might stay put to prevent collapse. If what you have left is reorganized or thickens in a manner that withstands biomechanical force; you potentially recover in a different way."
Agarwal is analyzing the bones of captive macaque monkeys with known life histories to gain insights into what drives bone reconfiguration. She relies on animals because bone scans that can be easily and safely conducted on humans do not reveal the interior details of trabecular bone.
The bottom line, says Agarwal, is to find better ways to prevent osteoporosis today. "I'm not saying that women should have ten babies and breast feed each for four years. But if we can identify the factors that are most important to maintain bone from an evolutionary and biocultural approach, we can experimentally figure out what to develop to address these problems."
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From Nanosolar to Spintronics
Michael Crommie, a Berkeley professor of physics (left) with graduate student Matt Comstock. The monitor depicts one of Crommie's experiments stimulating molecules with laser light. Image credit: courtesy Michael Crommie
Atoms and molecules may be tiny, but they hold big promise to Michael Crommie. A Berkeley professor of physics, Crommie envisions a day when molecular machines, quantum computers, and molecule-sized solar cells are commonplace. To turn these dreams into reality, Crommie is uncovering the principles that govern the behavior of nanoscale structures.
"I'm interested in how we can create very small structures and control them, and to understand the mechanisms that make them behave the way they do," Crommie says.
His quest isn't going to be easy. The world operates very differently at the nanoscale, where objects are on the order of one billionth of a meter in size. Here, the often mind-bending rules of quantum physics govern the properties of individual molecules.
That's particularly true for nanomagnets. Magnets the size of a single atom are attracted to iron filings in the same way as a standard horseshoe magnet. But that's where the resemblance ends. "Unlike the magnet you stick on your refrigerator door, which has a magnetic field that can point in any direction, the magnetic field of nanomagnets can only point in discrete directions. In other words, they are quantized," Crommie says.
A copper surface with triangular cobalt islands interspersed. Green specks on the islands are individual iron atoms. The map was obtained with a spin-polarized scanning tunneling microscope, which measured the spin of each iron atom—a feat Crommie's laboratory was the first to accomplish. The size of the image is 36nm x 36nm. Image credit: courtesy Michael Crommie
Configuring nanomagnets in rows or other two-dimensional arrays can alter their electromagnetic properties in unexpected ways, says Crommie. One configuration might align the electron spins of each nanomagnet all in the same direction, making the array a "ferromagnet," while another arrangement might cause the spins to align antiparallel, forming an "anti-ferromagnet."
Crommie is exploring how to link the magnetic spins of nanomagnets by combining them with other materials. Recently, he and his collaborators took two vanadium atoms and linked their spins together through a single organic molecule called tetracyanoethylene. "We were able to detect the coupling between the spins; one influenced the other through the molecule," Crommie says. "This is an important step forward in the creation of larger quantum spin structures and networks."
Being able to predict and control these properties could lead to a whole new paradigm for electronic devices. Where today's electronic circuits use electric fields to create regions that encourage or discourage the flow of electrons, new "spintronic" circuits might control these pathways via the alignment of nanomagnets. Spintronic circuits could potentially be smaller, generate less heat, and be better adapted for many applications.
One of those is quantum computing. "In a classical computer, the bits represent either zero or one, on or off. But in a quantum computer, they could be zero or one at the same time. So you can encode much more information in the bits. That is potentially vastly more efficient than classical computers for problems such as data encryption."
A chain of nanophotovoltaic molecules on a gold surface as imaged by a scanning tunneling microscope. Seven molecules can be seen in the chain, each of which is designed to behave as a solar cell. The image is a result of a research collaboration between the Crommie, Segalman, and Tilley research groups at UC Berkeley. Image credit: courtesy Michael Crommie
The electrical properties of atoms are equally central to another of Crommie's projects: creating solar cells the size of a single molecule. This work is part of the Lawrence Berkeley Laboratory Helios Project, which seeks to develop the means to perform artificial photosynthesis. "The idea is to find new ways to convert sunlight to fuel," Crommie says.
The solar cells people currently use work well, but the panels themselves are expensive to manufacture and difficult to mass produce. Crommie and his coworkers want to replace them with nanostructures such as photovoltaic organic molecules. These nanosolar cells might be simply sprayed onto surfaces, and mass produced cheaply.
Others have created molecular aggregates capable of converting sunlight into electricity, but these are extremely inefficient. Crommie suspects much of the problem stems from the large number of disordered interfaces an electron must navigate in these nanophotovoltaic structures. He is currently exploring photovoltaic processes down at the single molecule level, from the absorption of photons to the transfer of electrons from one molecule to another, and he hopes to eventually optimize this process.
Nanoscale research demands special equipment and laboratories insulated from vibrations, electrical fields, temperature shifts, and even acoustical noise. In search of better experimental conditions, he says, "the Physics Department has been upgrading the labs that we have, but it's not enough. We need new labs."
To that end, Crommie and others have secured an $11 million grant from the Department of Commerce to build a state-of-the-art laboratory for nanoscale research on campus. The laboratory will encompass 10,000 square feet in the basement of a new Campbell Hall, constructed when the current, seismically vulnerable building is torn down. Crommie, for one, can't wait.
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Shopping the Biological Bazaar
Ellen Simms also served as Director of the UC Botanical Garden from 1998 to 2003. Image credit: Thomas Colton
To fast-moving humans, plants can appear as passive as the soil they grow in. But such judgments do plants a grave disservice. To survive in the wild, says Ellen Simms, a Berkeley professor of integrative biology, plants amass allies, adjust their behavior and maneuver for advantage like all other organisms.
"They're involved in the same kinds of negotiations and give and take with their partners in nature as humans are," Simms says.
Simms studies mutualisms—where individuals of different species help one another so that both benefit—among plants and their ecological communities. Her goal is to examine how mutualisms influence evolution in natural populations.
Scientists have identified many potential plant mutualisms in nature. For example, ants colonize plants that provide nutritional rewards called food bodies. Without ants, these plants get devoured by herbivores. However, the relationship might not be so equal: the ant colony might be just as well fed and successful living elsewhere.
Bradyrhizobium bacteria, which live both free in soil and in the roots of legumes, can take nitrogen in air and transform it into a chemical form that plants can use as fertilizer. Image credit: Ellen Simms
"Early in this work, I realized there were a lot of 'just so' stories about mutualistic interactions, but people rarely tested if the assumptions were valid," Simms says.
Simms avoids those pitfalls by investigating partnerships where the benefits can be clearly measured for both parties. Her current research involves plants called legumes and nitrogen-fixing bacteria. Peas, alfalfa and other legumes grow root nodules to house these microbial helpers. In exchange for sugars and a place to live, the bacteria transform the nitrogen in air into fertilizer. Air is made up of several elements besides oxygen; nitrogen is among them. Legumes regulate the amount of air reaching their nodules and nitrogen-fixing bacteria.
When a legume seed sprouts, it must recruit its colonies of nitrogen-fixing bacteria from scratch. "Right away that's a recipe for disaster for the plant. The plant encounters lots of different genotypes of bacteria in the soil, so it has to figure out which are the good ones," Simms says. She compares these dealings to traders in a market, where everyone seeks the best deal for herself.
Plants in the legume family harbor colonies of nitrogen-fixing bacteria in root nodules such as these from Lupinus arboreus. Image credit: Ellen Simms
To determine how legumes select appropriate strains of bacteria, Simms marries old-fashioned, get-your-hands-dirty greenhouse work with cutting edge genetic analysis. She is connecting the genes that bacteria carry with their phenotypes, or observable traits, especially their influence on plants.
One way in which legumes find useful microbes is by employing molecules on their roots that fit receptors on rhizobia like a lock and key. "But the genes involved in those mechanisms are not the ones involved in nitrogen fixation. So there's the possibility a bacterium with a bad nitrogen fixation gene with the right key can get into a plant's roots, and then the plant might be stuck," Simms says.
Lupines and the much smaller native legume trefoil (Lotus strigosus) engage in complex interactions with nitrogen fixing bacteria at Bodega Marine Reserve in Sonoma County. Among the plants Simms studies are these yellow bush lupine, Lupinus arboreus, overlooking Salmon Creek Beach at the reserve. Image credit: Ellen Simms
Legumes, Simms finds, use several techniques to discourage such cheaters. When she inoculated plants with both industrious nitrogen fixers and lazier microbes, the plants grew bigger nodules for the harder workers. And larger nodules, Simms has shown, contain more bacteria, a direct benefit. "The plant has a way of evaluating how much nitrogen it's getting from a nodule and rewards each accordingly," Simms concludes.
Simms is now investigating legume-microbe relationships in the wild. The dunes at Bodega Marine Reserve near Mendocino are populated by two native legumes, lupines and trefoils. Both interact with nitrogen-fixing Bradyrhizobium bacteria.
With a combination of genetic sequencing data and good old-fashioned greenhouse work, Simms found that the bacteria in trefoil roots can also benefit lupines. By contrast, lupine bacteria can nodulate trefoils but don't provide any nitrogen.
Bacteria aren't the only organisms that have close relationships with plants. Bumblebees such as this one visiting a varicolored lupine, Lupinus variicolor, are among dozens of insects and other species found to interact with lupines. Image credit: Ellen Simms
Since the lotus is at a disadvantage, Simms wondered, how are they able to persist? She then realized that almost all of the trefoils were found within a zone of shifting, sandy dunes, while lupines were more likely to grow amid older, more stable dunes containing more nutrients. "It turns out that what we thought of as lotus bacteria are really new dune bacteria, and the others are old dune bacteria," she says.
"We're starting to widen our perspective and realize that because there are other partners out there engaging in their own interactions, what is beneficial to one host is not necessarily beneficial to the other," Simms says. In other words, biological partners don't just interact in pairs as described in textbooks: they exist within interconnected communities, where one organism's relationships affect the presence and success of others, and all are overlaid by the demands of the environment.
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