This month’s Science Roundup is sponsored by:

Subaru VIP Partners Program
AAAS Members save between $1,300 - $3,300 off the manufacturer’s suggested retail price (depending on model and accessories) on the purchase or lease of a new Subaru from participating dealers. Please contact AAAS Member Services at 202-326-6417 or e-mail membership@aaas.org BEFORE visiting your local Subaru dealer. Access subaru.com to find a nearby dealer or learn more about Subaru vehicles.

Challenges in Immunology
Special Online Collection

Our rate of progress in understanding the immune system has been anything but sluggish over the past few decades. Yet despite the brisk pace of discovery and some enticing glimpses of how the immune system might be manipulated for therapeutic purposes, much is left to explore about its inner workings. A special section of the 3 Aug 2007 Science highlighted some of the outstanding challenges. A collection of Perspective articles discussed topics of active immunology research from human primary immunodeficiencies to lymphocyte function and development, while two News stories described efforts to thwart HIV using gene therapy and to unlock the mysteries of mast cells. In Science’s Signal Transduction Knowledge Environment (STKE), Review and Perspective articles discussed the signals involved in controlling T cell fate, T cell responsiveness, and local inflammatory responses mediated by the cytokine interleukin-17.


Ancient Protein Resurrection

Equipped with genome data and field observations of organisms from microbes to mammals, biologists have made big strides toward understanding the mechanisms by which living creatures evolve. Now, a 16 Aug Report published online on Science Express offers a fascinating glimpse of how evolution works at the molecular level. Last year, researchers re-created the genetic sequence encoding a 450-million-year-old protein -- the precursor of two vertebrate steroid hormone receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) -- and regenerated the protein by cloning the gene into cultured cells. Building on that work, Ortlund et al. now report on the x-ray crystal structure of that ancestral receptor and the steps that enabled it to take on new modern functions. Using structural, phylogenetic, and functional analysis, the researchers identified a specific set of historical mutations that recapitulate the evolution of GR’s hormone specificity for cortisol from an MR-like ancestor that bound deoxycorticosterone and aldosterone, but had only moderate sensitivity to cortisol. No single one of the mutations on its own transformed the ancestral receptor into a GR-like receptor, but in concert, they functioned to reposition crucial amino acid residues to create new receptor-ligand and intraprotein contacts. As noted in a related News story by R. F. Service in the 17 Aug issue, "the work underscores how chance mutations that seemingly add little value initially can help set the stage for major evolutionary leaps."


Clues to Worm Longevity

In 1993, scientists discovered that Caenorhabditis elegans worms with a mutation in the daf-2 gene -- which encodes an insulin receptor-like protein that regulates metabolism, development, and aging -- can live twice as long as normal worms. Since then, researchers have been searching for molecular clues to what makes these mutants live so long. In a study reported in the 3 Aug 2007 Science, Dong et al. used mass spectrometry to look for quantitative differences in protein levels in daf-2 mutants relative to wild-type worms. They identified 47 proteins that were more abundant in mutant worms and 39 proteins that were less abundant. Interestingly, genetic experiments revealed that not all of the protein changes in the daf-2 mutant are beneficial for life span. Rather, the results suggest that there may be a mix of pathways in daf-2 mutants that either increase or decrease life span, with the net effect being positive. As noted in an accompanying Perspective by S. K. Kim, "[n]ow that proteomics approaches are beginning to define molecular changes associated with extreme longevity, a future challenge will be to understand how the myriad changes interact to double life span in C. elegans."


Separating Body from Self

Out-of-body experiences -- feelings of being outside of one’s physical body -- are often reported by patients after severe and sudden injury, and by people who suffer from migraine headaches, epilepsy, and other neurological conditions. In the 24 Aug 2007 Science, two independent studies revealed methods for inducing elements of this sensation in healthy volunteers. Ehrsson and Lenggenhager et al. both used virtual reality goggles to give people a different perspective on their own bodies and drew upon the sense of touch to enhance the illusion. In separate but similar set-ups, cameras created the illusion that participants could see their own backs from a distance. When the researchers used a stick or rod to simultaneous touch the subjects’ physical body and their virtual body, subjects reliably reported the sensation of momentarily inhabiting the virtual body. In addition, subjects reacted autonomically in response to harm directed at their virtual body and displaced their bodily sense of self toward their virtual selves and away from their physical body. Both reports show that visual perspective and coordination between the senses of vision and touch are important for the sensation of being within the body, and could lead to a better understanding of how the brain generates the concept of self. An accompanying News story by G. Miller highlighted the studies.


When Fear is Near

The ability to evaluate threats in the environment and then coordinate appropriate behavioral responses to avoid or mitigate harm is important to an organism’s survival. Imminent threats and remote threats produce different behavioral responses, and many animal studies suggest that the brain systems that organize defensive behaviors differ accordingly. In a Report in the 24 Aug 2007 Science, Mobbs et al. used functional magnetic resonance imaging (fMRI) to investigate the neural dynamics of threat in humans. The team examined the brain activity in 14 healthy subjects as they navigated through a computerized maze, trying to avoid a "virtual predator" that had the capacity to chase, capture, and cause pain (in the form of shocks of varying intensity). The results show that as a predatory threat approaches, neural activity shifts from forebrain regions associated with value-based and complex decision making (such as the prefrontal cortex) to low-level midbrain regions implicated in reflexive escape behavior (e.g., the periaqueductal gray). As noted in an accompanying Perspective by S. Maren, "[b]y pinpointing these specific brain circuits, we may gain a better understanding of the neural mechanisms underlying pathological fear, such as chronic anxiety and panic disorders." Lead author Dr. Mobbs also discussed the findings in a related podcast interview.


Conservation Successes

As global threats to Earth’s biodiversity -- from climate change to habitat destruction -- continue to accelerate, conservationists are racing to protect the planet’s endangered species. This month in Science, a trio of studies showcased conservation success stories on three continents that may point the way to future victories for threatened animals and plants. In a Brevium in the 10 Aug issue, Grenier et al. reported on the recovery of the black-footed ferret, the most endangered mammal species in North America. The population had declined to a low of just 5 animals in 1997, but thanks to a program of captive breeding and re-release into the wild, the ferrets are now recovering rapidly in Wyoming’s Shirley Basin, where they number more than 200. The researchers point to the species’ high initial survival and fertility as key to its recovery. In a Report in the same issue, Donald et al. highlighted the success of the European Union’s Bird Directive, an initiative instituted in 1979 to help protect rare or vulnerable bird species. Comparative analysis of bird inventories from 1970 to 1990 with those from 1990 to 2000 revealed positive population changes among targeted species relative to non-targeted species. There was also a strong correlation between the percentage of land each E.U. country set aside as protection areas and the overall success of the birds. Finally, a Report in the 31 Aug issue (published online Science Express on 9 Aug) by Oliveira et al. presented the results of fine-scale satellite monitoring of deforestation and logging in the Peruvian Amazon. The team reports that a relatively small percentage of the detected damage between 1999 and 2005 occurred within natural protected areas or indigenous territories, which suggests that land-use and conservation policies have been effective in reducing forest losses. A related ScienceNOW story by M. Balter published 9 Aug highlighted the studies.


Early Near East Urbanism

Southern Mesopotamia, a part of present-day Iraq, has long been considered the birthplace of humanity’s cities and a model of how those first cities emerged and expanded. Now, in a Brevium in the 31 Aug 2007 Science, Ur et al. describe new evidence of a sprawling urban center in northeastern Syria whose origins and breadth rival that of contemporary settlements to the south. The age and distribution of artifacts at the ancient site known as Tell Brak indicate that a large urban area existed there in the 5th and 4th millennia before the common era (BCE), but the spatial patterning of its growth diverges from the southern Mesopotamian model. Rather than growing from a populated center outward, Tell Brak began as clusters of small settlements interspersed with empty spaces, and then eventually grew more dense as it expanded inward. According to the researchers, this pattern suggests a greater role for noncentralized social and political processes in the initial growth of Brak, and a lesser importance for centralized authority. A related News Focus by A. Lawler highlighted the study and other independent and revealing evidence of the size and sophistication of the Tell Brak settlement.


Attosecond Spectroscopy
Special Online Collection

The precision attainable in timing events once depended on how fast a human being could press the button on a stopwatch. Pulsed laser sources have since taken the place of those hand-held devices for measuring the fastest of phenomena. Advances in laser technology over the past several years have fueled the emergence of attosecond science -- the study of physical processes such as electron motions that occur in less than a fraction of a cycle of visible light, on the order of a few billionths of a billionth of a second. Three Review articles in the 10 Aug 2007 Science highlighted the methods underlying attosecond science and the prospects for future applications. Bucksbaum explained how attosecond pulses of light are made and measured and explained what events such light pulses can be used to track, from electron rearrangements in chemical bonding to conduction dynamics in metallic solids. Goulielmakis et al. reviewed the current state and future of lightwave electronics, in which controlled light waves can steer electrons inside and around atoms. And Kapteyn et al. described efforts to harness attosecond science to generate coherent x-rays for diffraction and imaging experiments.


Water Aids Toxin Synthesis

Ladder polyethers -- long, ladderlike toxins produced by marine microbes called dinoflagellates -- contribute to harmful algal blooms known as red tides. Their distinctive molecular architecture and potent lethality to marine life have motivated efforts to chemically synthesize them for the last 20 years. The leading hypothesis has been that dinoflagellates create the compounds by launching a cascade of reactions that open small ring compounds called epoxides, each of which contains an oxygen atom bound to two carbons, as the first step to adding successive rings to the ladder. In practice, however, opening the epoxides produces an unwanted compound and geometry, and directing the correct reaction has required the addition of numerous unnatural substituents. Now, in a Research Article in the 31 Aug 2007 Science, Vilotijevic et al. report that the problem as been the focus on organic solvents in which to perform the requisite reactions. The researchers show that neutral water is an optimal promoter for the ring-opening reaction and offers a high-yield route to the naturally occurring ladder core. The new work underscores the likely importance of aqueous-medium effects to certain enzymatic selectivities. An accompanying News story by R. F. Service highlighted the study.


Controlling Micelle Formation

Covalently connecting two distinct polymer segments at their ends results in the formation of a class of hybrid macromolecules called block copolymers. When placed in a solvent in which one segment is soluble and the other is not, these polymer molecules will self-assemble into clusters called micelles, whose structural and chemical diversity make them attractive for use in applications such as drug delivery and nanolithography. These applications require that micelle size, shape, and chemical structure be precisely controlled, and two Reports in the 3 Aug 2007 Science describe important advances toward this goal. Wang et al. showed that the length and composition of cylindrical micelles can be controlled by the addition of more dissolved block copolymers in a process analogous to the growth of living polymeric chains. By adding different block copolymer, they were able to form hybrid "co-micelles". Meanwhile, Cui et al. described a general strategy for the generation of complex, one-dimensional nanostructures from block copolymers. The technique relies on solvent mixtures and organic counterions to drive the organization of the block copolymers down specific pathways, resulting in supramolecular assemblies with distinct morphologies and chemical compositions. An accompanying Perspective by M. A. Hillmyer highlighted the studies.


Variable Ocean Circulation

The Atlantic meridional overturning circulation (MOC) carries warm, shallow water northward to high latitudes and returns cold, deep waters southward across the Equator, thereby transporting substantial amounts of heat throughout the ocean system. Global climate models have suggested that the flux of water transported might be decreased by global warming, which could have a profound effect on climate, particularly in Europe, but the lack of long-term and detailed observational records has made it difficult to evaluate whether a significant shift has occurred. Two Reports in the 17 Aug 2007 Science now offer annual records of the strength of the MOC using the Rapid Climate Change mooring array -- a collection of anchored instruments deployed across the Atlantic at 26.5 degrees N latitude that measure bottom pressure, temperature, and salinity. Cunningham et al. defined the size and structure of the intra-annual variability of the MOC and found that the different components forming deep water in the North Atlantic varied in intensity by a factor of eight over the course of a year. According to Kanzow et al., fluctuations of the different transport components largely compensate for one another, which means that robust estimates of the MOC can be made over intra-annual periods. J. Church discussed the findings and the importance of continued long-term monitoring in a related Perspective and podcast interview.


Improved Climate Predictions

A common criticism of global climate models is that they are overly simplistic, including external forcing factors such as solar radiation and the concentrations of greenhouse gases, but neglecting to incorporate the effects of natural changes within the climate system such as El Nino and fluctuations in ocean circulation. In a Report in the 10 Aug 2007 Science, Smith et al. presented a new modeling system that takes into account both internal variability and externally forced changes. As a result, the model can forecast surface temperature with substantially improved skill over a decade, both regionally and globally. According to the new model, internal variability will partially offset anthropogenic global warming for the next few years, but climate will continue to warm, with at least half of the years after 2009 predicted to be warmer than 1998 -- the warmest year currently on record. A related News Focus by R. A. Kerr highlighted the Report as well as the efforts of other researchers to gauge the effects of natural climate variations and model their impacts on future climate.


Uranus’ Rings, Edge On

Once every 42 years, the angle between Uranus and the Earth lines up such that the planet’s rings can be seen edge on, with the Sun and the Earth on opposite sides of the ring plane. This year marked the first time this rare alignment has occurred since the rings were discovered in 1977, and thus provided a rare opportunity to observe the dark (unlit) side of the rings, where dense rings darken to near invisibility, but faint rings become much brighter. In a Report published online Science Express on 23 Aug 2007, de Pater et al. presented a ground-based infrared image of this dark side, which shows that the system has changed dramatically since previous views. A broad cloud of faint material, likely dust, permeates the system but appears to be unconnected with any particular ring or feature. Although some differences can be explained by the unusual viewing angle, the researchers conclude that the dust distribution within the system has changed significantly since an encounter with the Voyager spacecraft in 1986 and occurs on much larger scales than has been seen in other planetary systems. Lead author on the study Dr. de Pater discussed the findings in the 24 Aug podcast.

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In Science’s STKE

Cells on the Move

The orchestration of cell movements is essential for a variety of functions, ranging from organogenesis to the immune response. In its 21 Aug 2007 issue, Science’s STKE reexamined the conventional wisdom concerning cell migration, and described new research that challenges some of the established models of various aspects of directed cell movement (see the Editorial Guide). In a Perspective, Perlin and Talbot explained how a single chemokine, signaling through two receptors, can elicit distinct responses in different populations of cells in the zebrafish lateral line primordium. Gupton and Gertler reviewed the established and novel proteins that mediate the formation and dynamics of filopodia (finger-like cellular protrusions composed of parallel bundles of actin filaments), different mechanisms of filopodium formation, and the various functions that distinct filopodia perform. And a Protocol by Wang et al. described a method to isolate the pseudopodium or "cellular feet" from the cell body, and then perform proteomic and analyses to identify the signaling pathways and proteins that mediate cell migration.

Also in STKE this month:
--McGehee discussed how nicotine’s modulation of synaptic plasticity in the prefrontal cortex may contribute to its effects on memory and reward circuitry (14 Aug 2007)
--Sumimoto et al. highlighted the structure and function of the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants (28 Aug 2007)
--Burch-Smith and Dinesh-Kumar discussed plant TIR (Toll-interleukin-1 receptor) domains which are used for pathogen detection, and possibly to direct the expression of genes involved in defense responses (28 Aug 2007)

This month’s Science Roundup is sponsored by:

Subaru VIP Partners Program
AAAS Members save between $1,300 - $3,300 off the manufacturer’s suggested retail price (depending on model and accessories) on the purchase or lease of a new Subaru from participating dealers. Please contact AAAS Member Services at 202-326-6417 or e-mail membership@aaas.org BEFORE visiting your local Subaru dealer. Access subaru.com to find a nearby dealer or learn more about Subaru vehicles.