PNAS News Archive: January 20 - January 24, 2003

  Selected articles appearing in PNAS the week of January 20 . . .
 

Our Ancestor, the Aardvark?

The African elephant and the aardvark both belong to superorder Afrotheria.

The ancestor to all placental mammals may have had a chromosome set similar to the modern-day aardvark, according to new research in an article published this week in PNAS. Aardvarks belong to a superorder of mammals known as the Afrotheria, a group thought to have evolved on Africa when that continent was isolated from the others through plate tectonics. While genetic research has supported the relatedness of animals in this superorder, scientists are still at odds over whether the placental mammal ancestor resides in the Afrotheria or another group. In this study,
T. J. Robinson at Stellenbosch University and colleagues compared chromosomes from three animals in the Afrotheria -- aardvarks, African elephants, and Asian elephants -- and humans, who are in a different superordinal group. The researchers found that all the organisms shared several chromosome sections, with the Afrotheria members having the most sections in common. Humans shared the greatest number of chromosome sections with aardvarks. In conjunction with previous data, these results suggest that aardvarks have the fewest chromosomal differences from other placental mammals, placing them closest to the last surviving placental mammal ancestor.

"Reciprocal chromosome painting between human, aardvark and elephant (superorder Afrotheria) reveals the likely Eutherian ancestral karyotype" by F. Yang, E. Z. Alkalaeva, P. L. Perelman, A. T. Pardini, W. R. Harrison, P. C. M. O'Brien, B. Fu, A. S. Graphodatsky, M. A. Ferguson-Smith, and T. J. Robinson

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Designer Molecule Targets Asthma

This molecule, known as PNRI-299, reduces lung inflammation associated with asthma.

Researchers have designed a novel molecule that reduces the inflammation associated with asthma. Asthmatics experience a complex inflammatory response in the lungs that produces swelling and mucus, reducing the ability to breathe. Described in an article published this week in PNAS, the synthetic molecule, named PNRI-299, inhibits a protein that leads to inflammation. Michael Kahn of the Pacific Northwest Research Institute and colleagues used an automated chemical process to develop and test a series of designer molecules that might inhibit production of AP-1, a protein that has a high activity in the bloodstream of some asthmatics. Using basic knowledge of the AP-1 structure, the authors constructed a pool of designer molecules, each with a slightly different molecular structure, and tested the ability of each molecule to inhibit AP-1 inside living cells. Once PNRI-299 was identified as an inhibitor, the authors tested it in a mouse model of asthma. The designer molecule reduced airway swelling and mucus secretion in the mouse. Searching for PNRI-299's target, the authors found that the molecule inhibits the action of an AP-1 activator, Ref-1. The work not only outlines an approach for testing small molecule therapeutics, but also identifies inhibition of Ref-1 as an important target in the treatment of asthma.

"Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma" by Cu Nguyen, Jia-Ling Teo, Akihisa Matsuda, Masakatsu Eguchi, Emil Y. Chi, William R. Henderson, Jr., and Michael Kahn

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For Multicellular Evolution, Cooperation Is Key

Multicellular life may have evolved partly to exclude selfish individuals from clusters of cooperative cells, according to new research in an article published this week in PNAS. Past research on multicellular evolution focused on division of labor as the main benefit of cells living in groups. However, Sebastian Bonhoeffer and Thomas Pfeiffer at ETH Zurich focused here on the motivation for cells to stick together before differentiating into distinct cell types. The scientists developed a computer simulation to test which category of cells, "fermentors" or "respirators," would have the greatest population increase over time when occupying the same environment. Fermentors have a fast rate of metabolism, but don't produce very much energy from a food source. Respirators have a slower rate of metabolism than fermentors, but produce more energy overall. In the first simulation, fermentors triumphed over respirators when both lived as individual cells. However, in further simulations where cells were allowed to clump, respirators had a decided advantage. Benefits to group members were greatest when cells were permitted to exchange resources through adjacent cell walls. The scientists suggest that because respirators produce energy more efficiently, group members living together suffer less competition and can survive on fewer resources. The finding may explain why many modern fermentors, such as yeast, live as unicellular creatures.

"An evolutionary scenario for the transition to undifferentiated multicellularity" by Thomas Pfeiffer and Sebastian Bonhoeffer

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Language Law Made Meaningful After 50 Years

New research suggests that a regularity common to most human languages, known as Zipf's law, results from an inherent tradeoff between a speaker's and a listener's needs. The law describes how the probability of word occurrence starts high and tapers off. In essence, a few words occur very frequently while many others occur rarely. Although Zipf's law was proposed more than half a century ago, the law's meaning has remained open to question. In an article published this week in PNAS, physicists Ramon Ferrer i Cancho of Universitat Pompeu Fabra and Ricard Sole of Santa Fe Institute propose a derivation of Zipf's law which lends it wider significance, by contrasting the communicative needs of speaker and listener. A listener prefers words to have clear and specific meanings, with each word assigned to one object or symbol. In contrast, it is easier for a speaker to retain a smaller vocabulary of vague, ambiguous words, where each word has many meanings. The physicists mathematically demonstrate that when these two extremes strike a balance, as they do in actual human language, Zipf's law emerges. The findings suggest that Zipf's law is a hallmark of symbolic reference and not simply a meaningless linguistic feature. The research might also help explain the discrepancy between human and animal language and the failures of artificial communication models.

"Least effort and the origins of scaling in human language" by Ramon Ferrer i Cancho and Ricard V. Sole

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Bone Marrow Cells Boost Brain

This brain cell from a female patient, marked with a red dot, contains a Y chromosome.

Human stem cells from bone marrow transplants can migrate into the brain and form new neurons, according to research published this week in PNAS. These findings could eventually inspire novel treatments for brain trauma and diseases such as Alzheimer's and Parkinson's. Using autopsy samples from female patients who received bone marrow transplants from male donors, Eva Mezey of the National Institute of Neurological Disorders and Stroke and colleagues searched brain tissue for cells containing a Y chromosome, an indicator that these cells were donor-derived. Each of the patients had many Y-positive brain cells, including neurons. The distribution of Y-positive brain cells was not random -- rather, the Y-positive cells were found in clumps, indicating that original donor cells had continued to multiply after differentiating into brain cells. Past research with animal models has shown that donor bone marrow stem cells can migrate throughout the body in the bloodstream, differentiating into various cell types. The researchers suggest that developing a way to direct these stem cells into areas where neurons are damaged or diseased could help repair the brain.

"Transplanted bone marrow generates new neurons in human brains" by Eva Mezey, Sharon Key, Georgia Vogelsang, Ildiko Szalayova, G. David Lange, and Barbara Crain

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New Breast Cancer Gene Discovered

A newly discovered protein secreted only by breast cancer and salivary gland cells may provide another point of attack against breast cancer, report Ira Pastan and colleagues at the National Cancer Institute in an article published this week in PNAS. The team found the protein by screening for RNA molecules that are overproduced by breast cancer cells, compared to healthy tissues such as liver and kidney. At the end of this search the researchers had over 3000 new RNA transcripts that are unrelated to any known genes, some of which may contribute to breast cancer. The authors further investigated the expression of one particular gene, called BASE (Breast cancer And Salivary gland Expression), which was present both in primary and metastatic cancer. Expression of the BASE gene was detected in many of the breast cancers examined, but never in normal tissues, except for salivary glands. The function of the BASE gene is not yet known, but its sequence suggests that it is secreted from the cell. Pastan's group suggests that BASE could be a useful diagnostic marker of breast cancer, as well as a potential target for vaccines.

"Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins" by Kristi A. Egland, James J. Vincent, Robert Strausberg, Byungkook Lee, and Ira Pastan

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