Bio-Med Roundup

This month in Science Roundup:


Exploring Undergraduate Education
Special Online Collection

Universities around the world differ greatly, but the challenges facing those who teach undergraduate science, technology, engineering, and math courses are surprisingly similar. In a special News section in the 6 Jul 2007 Science, profiles of a dozen faculty members from around the globe highlighted some of the common challenges in promoting values of scientific thinking and knowledge despite vast regional differences in student makeup, education policies, and cultural and economic backgrounds. And in a roundtable interview, accompanied by a full-length audio recording, three U.S. educators described their efforts to improve undergraduate science education. In conjunction with the special issue, the Signal Transduction Knowledge Environment featured three new Teaching Resources and debuted the STKE Journal Club, devoted specifically to graduate student- or postdoc-authored commentary highlighting current signal transduction research. Finally, a collection of articles on ScienceCareers.org focused on issues important to undergraduates, including opportunities for research experience and funding.


Sea Anemone Genome Surprises

Researchers have previously relied on the sequenced genomes of the fruit fly, nematode worm, and a few other invertebrates to understand animal evolution leading up to the vertebrates. Now, in a Research Article in the 6 Jul 2007 Science, Putnam et al. report surprising new revelations from the genome of a seemingly simple sea creature -- the starlet sea anemone Nematostella vectensis. Sea anemones, along with corals, jellyfish, and hydras, constitute the oldest phylum of eumetazoans, which comprise all animals except sponges. Despite the anemone’s apparent morphological simplicity -- a sac-like body plan with a single oral opening, two tissues layers rather than three, and a rudimentary nerve net as opposed to a central nervous system -- it has a complex genome, with a gene repertoire of about 18,000 genes whose identity, structure, and organization within the genome are more similar to vertebrates than to flies or nematodes. Blocks of DNA have the same complement of genes as in the human genome and more than 80% of the anemone introns (DNA sequences that interrupt the protein-coding sequences of a gene) are in the same places in humans, suggesting that they probably existed in a common ancestor about 700 million years ago. As noted in an accompanying News story by E. Pennisi, these insights imply that "even very ancient genomes were quite complex and contained most of the genes necessary to build today’s most sophisticated multicellular creatures."


Possible Parkinson’s Lead

Several neurodegenerative disorders associated with protein misfolding are also intimately tied into aging. Biological pathways involved in aging may thus provide targets for therapeutic intervention in these diseases. In a Report in the 27 Jul 2007 Science Outeiro et al. identified a compound that can modulate the toxicity and aggregation of alpha-synuclein, a protein associated with Parkinson’s disease. The compound selectively inhibits the activity of sirtuin 2 (SIRT2), one of a family of proteins called histone deacetylases that participate in a variety of cellular functions and play a role in aging. The inhibitor protected neuronal cells against cell death both in vitro and in a fly model of Parkinson’s disease. Genetic inhibition of SIRT2 by RNA interference similarly protected against alpha-synuclein toxicity. Interestingly, the SIRT2 inhibitor increased the size of alpha-synuclein aggregrates in a cellular model of the disease, an effect that might help reduce aberrant interactions of aggregates with cellular proteins. As noted in an accompanying Perspective by A. Dillin and J. W. Kelly, "[t]he study not only identifies SIRT2 as a potential new target for Parkinson’s disease intervention, but also bolsters recent work linking age-related cell signaling pathways to protein aggregation processes and age-onset neurodegenerative diseases."


Tackling HIV, Genome-Wide

The body’s first response to HIV strongly influences how fast the virus will destroy the immune system and can vary widely among infected individuals. One particularly striking and largely unexplained difference among patients during the early stages of infection is the viral set point -- the level of circulating virus in the blood during the non-symptomatic phase preceding progression to AIDS. In a Report published online Science Express on 19 Jul 2007, Fellay et al. aimed to identify human genetic differences that influence this variation. Using a whole-genome association strategy that involved 486 patients, the team identified two immune-related polymorphisms (genetic variants) that together can explain about 15% of the total variation seen in the viral set point of patients. One of the polymorphisms, which correlates with a low viral set point, is associated with a rare gene that codes for a protein on immune cells that plays a central role in clearing the body of HIV-infected cells. A third variant was found in a region upstream of a gene that encodes an RNA polymerase subunit, though the mechanism by which it might influence disease progression is unclear. Similar genome association analyses may provide important insights into patient susceptibility and resistance to other infectious disease. A related ScienceNOW story by J. Cohen highlighted the study.


Suppressing Memories

For decades, psychologists have debated whether or not the brain can suppress unwanted memories, and if so, how. In a Research Article in the 13 Jul 2007 Science, Depue et al. tackled this long-standing question by using functional magnetic resonance imaging (fMRI). In the training phase of a memory experiment, volunteers were shown pairs of neutral faces and negative pictures (such as a car crash) and asked to memorize which face went with which picture. In the subsequent experimental phase, brain activity was recorded while participants viewed only the face. On some trials they were asked to recall the previously associated picture, while on other trials they were instructed to actively block the associated picture from coming into memory. Results from a final testing step revealed that people can effectively suppress memory. The fMRI data further suggest that this process is controlled or modulated by two specific areas of the prefrontal cortex (PFC) in two different steps. First, one area of the PFC suppresses brain regions involved in the sensory aspects of memory including the visual cortex. Then, a different part of the PFC suppresses brain regions that support memory processes and emotional associations with memories. Dr. Depue discussed the work and its implications for understanding and treating disorders involving the inability to suppress unwanted thoughts -- such as post traumatic stress disorder, phobias, and depression -- in a related podcast segment.


Overlooked Pollutants

Organic compounds such as dioxin, DDT, and PCBs (polychlorinated biphenyls) are among the world’s most toxic substances: they do not break down easily, and owing to their fat solubility, can build up or "biomagnify" in food chains, causing adverse health effects in wildlife and in humans. Regulatory authorities currently identify these so-called persistent organic pollutants (POPs) based on their hydrophobicity and measures of their accumulation in fish food webs. But results from a new study suggest that this system could be missing an entire class of potentially dangerous chemicals. Kelly et al. measured the contaminant levels for various animals in aquatic and terrestrial food webs in northern Canada, and compared their data with bioaccumulation modeling studies. Their results show that poorly metabolizable, moderately hydrophobic substances that do not biomagnify in aquatic food webs can accumulate to a high degree in food webs containing air-breathing animals including humans. The team attributes this difference to the slow rate of respiratory elimination in air-breathing animals. That is, many chemicals that that are relatively soluble in water and therefore don’t accumulate in fish might remain in the tissues of land animals if they cannot be released from the lungs to the air. J. Kaiser highlighted the new findings, and their potential implications for current regulatory assessments, in a related News story and podcast interview.


Absorbent Aerogels

Porous inorganic materials are widely used as molecular sieves, ion exchangers, and catalysts. Although these materials can vary in the number, size, and distribution of pores, they are typically oxides and have limited applications because oxides preferentially form bonds with small metal ions such as magnesium and zinc. In a Report in the 27 Jul 2007 Science Bag et al. reported on the creation of a new type of porous material that can absorb heavy metals such as mercury and could therefore be useful for applications such as environmental remediation. Using small clusters of metal chalcogenides instead of oxides -- in which sulfur or selenium take the place of oxygen -- and platinum ions as linkers, the researchers constructed porous aerogels that are semiconducting, have high surface areas, and preferentially bind heavy metals ions. The gels can absorb large quantities of mercury ions from solution as well as nonpolar organic molecules. As noted in an accompanying Perspective by S. L. Brock, "[w]hether chalcogenide aerogels will find practical applications remains an unanswered questions, although the few studies on these materials have yielded provocative results."


Checkers: It’s a Draw

Solving the game of checkers -- determining the final result in a game with no mistakes made by either player -- is a daunting task. Compared with the 765 possible positions placements of X’s and O’s in a game of tic-tac-toe, there are roughly 500 billion billion possible moves in a battle of checkers. Since 1989, almost continuously, dozens of computers have been working on solving the game, applying state-of-the-art artificial intelligence techniques. Now, in a Research Article published online Science Express 19 Jul 2007, Schaeffer et al. report what grandmaster players have conjectured for decades: If two opponents execute perfect play, the game will inevitably end in a draw. The team began by constructing a database of all 39 trillion possible arrangements with 10 or fewer pieces on the board. In the process, they determined whether each one led to a win for black, a win for red, or a draw. They then considered the very beginning of the game, opened with a move by black, and then used a specialized search algorithm to trace out subsequent moves. As the two players try to maximize their advantage, they inevitably steer the game to one of the 10-checker configurations that leads to a draw. An accompanying News story by A. Cho in the 20 Jul issue highlighted the study.


Greenland’s Greener Past

The environmental histories of high-latitude regions such as Greenland are poorly understood because much of the fossil evidence is hidden beneath kilometer-thick sheets of ice. But a Report in the 6 Jul 2007 Science now shows that clues about these paleoenvironments can be extracted from another source -- ancient DNA trapped within deep ice cores. Willerslev et al. were able to extract and amplify DNA from ancient plant and animal remains recovered from the silty bottom sections of 2- to 3-kilometer-deep Greenland ice cores. Their analysis reveals that high-latitude southern Greenland, which currently lies below more than 2 km of ice, was once covered by a diverse boreal forest that included pine, spruce and alder trees, herbaceous plants, and that was inhabited by insects such as beetles and butterflies. Although the dating of ice cores that deep remains uncertain, several methods suggest that the silty ice and its forest community predate the last interglacial period (Eemian) about 130,000 to 116,000 years ago and may be up to 800,000 years old. Recovering genetic data from basal ice may enable environmental reconstructions of other ice-covered areas and yield insights into the climate and the ecology of communities from the distant past. A related News story by A. Curry profiled the ambitious lead author of the study.


Stellar Surface Revealed

Imaging the surfaces of stars other than the Sun promises to advance our knowledge of the physical processes at work on them. But even the strongest telescopes have been inadequate at resolving the details of these celestial bodies. Now, in a Report in the 20 Jul 2007 Science (published online 31 May), Monnier et al. report the use of advanced optical interferometric techniques to capture unprecedented images of a stellar surface. By combining and processing near-infrared light from four separate telescopes the team was able to construct an image of the surface of Altair, one of the brightest stars in the night sky. The images confirm that this hot and rapidly rotating star is elongated in shape due to centrifugal forces, with poles that are hotter than the equator. However, the amount of distortion and changes in surface temperature diverge from standard models of stellar rotation, suggesting that differential rotation and/or other physical processes may also be involved. As noted in an accompanying Perspective by A. Quirrenbach, further advances in interferometry could reveal even more details about stellar surfaces such as star spots, eruptions, and convection patterns.


Modeling National Development

Economies grow by upgrading the products they produce and export. However, the technology, capital, institutions, and skills needed to produce newer products are more easily adapted from some products than from others. In a Research Article in the 27 Aug 2007 Science, Hidalgo et al. used network theories and international trade data to build a dynamic model of country growth and development based on the relatedness between products or "product space." The model maps goods that require similar skills, infrastructure, etc. to produce -- like apples and pears, for example -- in close proximity to each other, whereas a product such as a home appliance that requires different capabilities to produce lies farther away in the product space. Further examination of the space shows that more-sophisticated products are located in a densely connected core whereas less-sophisticated products occupy a less-connected periphery. Empirically, countries move through the product space by developing goods close to those they currently produce. This means that poorer countries tend to be located in the periphery, where moving toward newer products is harder to achieve. This pattern may help explain in part why some countries continue to grow economically while others remain stagnant.

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In Science’s STKE

The Two Sides of Epo

Erythropoietin or Epo is a glycoprotein hormone that is the primary regulator of red blood cell production. In its pharmaceutical forms, epoetin and darbepoetin, Epo is widely used to treat various anemias, including those associated with cancer. It acts through its cognate receptor on blood progenitor cells, triggering an array of signaling pathways that inhibit apoptosis and promote cell proliferation and differentiation. In a Perspective in the 17 Jul 2007 issue, A. J. Sytkowski discussed experiments supporting an action of Epo outside the hematopoietic system. Specifically, several groups of researchers have discovered a "tissue-protective," antiapoptotic effect of Epo on neural and other tissues. These results have led some to question if this effect could extend to cancer cells, even those subjected to chemotherapy or radiotherapy. Determining whether therapeutic doses of Epo can indeed stimulate the growth of certain cancers will clearly have crucial implications for current cancer treatment regimes.

Also in STKE this month:

--Mohapatra et al. highlighted the recently discovered role of the voltage-gated potassium channel Kv2.1 in facilitating neuropeptide release, independent of its ion-conducting function ( 3 Jul 2007)
--Van Haastert and Veltman discussed the multiple signaling pathways involved in chemotaxis ( 24 Jul 2007)
--Qi and August discussed the function of the adapter protein SLP-76 during T cell activation ( 24 Jul 2007)