Yale Alumni Magazine: Findings

The human species didn't emerge until about 65 million years after the last of the dinosaurs died out. But a new fossil analysis suggests that our earliest primate ancestors were on the scene almost immediately after that great extinction. Like many primates today, they were tree-dwelling omnivores with an apparent preference for fruit. Unlike living primates, however, they had eyes that faced in different directions. And they were so small that one of their skulls could fit on the pad of your index finger.

The animals are known as plesiadapiforms, and their place on the evolutionary tree has been debated for decades. Some scientists believe that plesiadapiforms were not primates, but close relatives of flying lemurs (which are not true lemurs). But an international team that includes Eric Sargis, associate professor of anthropology, cast doubt on that hypothesis recently by applying comparative anatomical analysis and high-resolution CT scanning to a collection of exceptionally well-preserved skeletons and skulls found in Wyoming limestone. Their report, which pushes the clock back 10 million years on primate evolution, appears in the January 23 Proceedings of the National Academy of Sciences.

Although the specimens don't have all of the characteristic primate features, certain cranial and dental features seem to unite them with primates, as do their grasping hands and feet. The study suggests an answer to a big question. "Features like grasping hands and feet, nails on digits instead of claws, and forward-facing eyes have often been proposed to have evolved in a single suite. What we're finding is that's not the case," says Sargis. "We can probably now say that grasping evolved before leaping, and before forward-facing eyes." Their study also supports the theory that the earliest primates co-evolved with flowering trees, developing the ability to grasp skinny branches in order to harvest fruit -- not to leap with forward-facing eyes in pursuit of insects, as some have hypothesized.

Nevertheless, there is no consensus yet. Paleontologist Christopher Beard, of the Carnegie Museum of Natural History, says the study is "not the last word." He contends that plesiadapiforms are closer to flying lemurs. "We need some fossil tree shrews and fossil flying lemurs that are about the same age as the oldest fossil primates," he says, in order to find out "how all these different lineages fit together." Sargis's collaborators have over 100 limestone blocks from Wyoming that may reveal more of the story.

In the 1966 sci-fi thriller Fantastic Voyage, a submarine and its crew were shrunk small enough to navigate through a diplomat's bloodstream. Forty years later, Yale scientists have developed devices so tiny that crew members of the Proteus couldn't have seen them without microscopes.

Mark Reed, the Harold Hodgkinson Professor of Engineering and Applied Science, and his colleagues have devised a way to create nanowires -- each about 5,000 times thinner than a human hair -- that can be integrated into already available microelectronic equipment. The resulting devices can detect responses in targeted immune cells almost as fast as they occur. "We electronically plugged into the biochemical system of cells," says Reed, whose report appeared in the February 1 Nature.

Such sensors could be used to detect proteins produced in minute quantities during the earliest stages of cancer and other diseases, when cures are more likely. These devices would not need the radioactive or fluorescent molecules currently used.

The researchers crafted the prototype nano-wire sensors by modifying materials and processes already in use in the semiconductor industry; earlier attempts to make such devices required methods that would have been difficult to mass-produce. Reed predicts the sensors will be available "in my lifetime." He's 52.

Obesity researchers thought they might have found their Holy Grail in the mid-1990s when they discovered the hormone leptin, which is secreted by fatty tissues in the body as a natural appetite suppressant. But weight-loss aids designed to affect the leptin pathway proved ineffective -- in part because some obese people become "leptin-resistant." Tamas Horvath, a professor of obstetrics and gynecology at the Yale School of Medicine, recently found that estrogen limits levels of body-fat storage in much the same way, raising hopes for estrogen-based weight-control drugs. Horvath's report was published in the online edition of Nature Medicine.

Horvath had long suspected estrogen might have an effect on appetite and weight. "In rodents, as well as in other animals, if you remove the gonads, they start to gain weight very quickly," he says. "But if you give those animals estrogen, they stop eating as much and their metabolism normalizes."

Horvath treated a group of mice with estrogen and examined their brains with electron microscopes. Just like leptin, estrogen increased the activity of neurons in a metabolism-controlling region of the hypothalamus, reorganizing synapses in a way that optimized appetite suppression and led to weight loss. This effect held true even in mice that lacked a leptin gene, suggesting that weight-control drugs that include estrogen might work even in leptin-resistant patients. Compromised estrogen signaling in the brain, Horvath believes, may be one reason many women experience a post-menopausal weight gain.

Wouldn't men experience feminizing side effects from an estrogen diet drug? No, says Horvath -- as long as brain-specific estrogen mimics were used. Nor would such compounds cause any of the problems associated with estrogen supplementation in women, such as cancer and heart disease. "You wouldn't have any of those health issues," says Horvath.

When it comes to choosing a mate, many female butterflies have two ways to assess a suitor's potential: sight and smell. But which sense is more important? To find out, Antonia Monteiro, an assistant professor of ecology and evolutionary biology, and graduate student Katie Costanzo worked with African butterflies belonging to the genus Bicyclus. In earlier research, Monteiro showed that it's the females that do the choosing.

In the Bicyclus mating game, females respond to male pheromones and to ultraviolet-reflecting dots in the center of the eyespots that adorn a male's forewings. To assess the relative importance of each, the researchers tried various combinations of cue-blocking: painting out the dots, for example, or plugging the androconia (the glands on the male hindwings that release the irresistible chemicals). They also painted the females' antennae to prevent them from picking up the male scent. Either cue, by itself, could lead to mating, Monteiro and Costanzo report in the January 2 online edition of the Proceedings of the Royal Society B. But, like handsome human males wearing the right cologne, "Bicyclus butterflies that displayed two cues were preferred to those with only one," says Monteiro.

During periods of fasting, humans and other animals have a way to keep the appetite up so that the body is primed to refuel when food again becomes plentiful. Yale School of Medicine neurobiologist Sabrina Diano and her colleagues recently isolated a molecular domino sequence that functions as a defense mechanism that the brain mounts during lean periods. Diano, an expert in the neural pathways that control the hunger response, had observed that when lab animals were fasting, their brain thyroid-hormone levels tended to be high. To determine what role the hormone played, Diano assembled three groups of mice: a group lacking an enzyme that controls thyroid hormone production in the brain; a group lacking a protein called UCP2 in a metabolism-regulating brain region; and a control group.

In the January issue of Cell Metabolism, the researchers report that when a fasting period begins, thyroid hormone levels in the brain rise, causing levels of UCP2 to spike. "The UCP2 protein induces an increasing number of mitochondria to form in the hypothalamus, which makes specific neurons in that area more active," she says. "These are the neurons that induce you to eat."

Diano thinks there's a sound evolutionary explanation for why bouts of the munchies may occur during periods of starvation. "Once you are finally introduced to some food, you want to eat as much as possible so that whenever another non-food phase comes around, you have more storage built up," she says. Diano hopes eventually to develop drugs that could curb appetite in overweight patients.