This month in Science Roundup


The Overlooked Epidemic
http://www.sciencemag.org/sciext/aidsamericas/

The HIV/AIDS epidemic in Latin America and the Caribbean has been overshadowed by the more severe problems in sub-Saharan Africa , the vastly larger population of Asia , and the widespread media attention and activism in more developed countries in North America and Europe . Nevertheless, an estimated 2 million people live with HIV/AIDS in the region. In a special News section in the 28 Jul 2006 issue, Science correspondent J. Cohen provided an in-depth look at the epidemics in 12 countries from Mexico to the Dominican Republic and discussed both the overlapping forces that are driving the spread of HIV, and some of the creative and aggressive efforts being made to combat them. A related Editorial by A. Fauci ( http://www.sciencemag.org/cgi/content/short/313/5786/409 ), director of the National Institute of Allergy and Infectious Diseases at NIH, highlighted the global challenges wrought by HIV/AIDS in the last 25 years. And on Science Online, a special multimedia presentation ( http://www.sciencemag.org/aidsvideo ) featured interviews with experts, maps, and video clips, and a slideshow of photographs by M. Linton ( http://www.sciencemag.org/sciext/aidsamericasshow/ ) documented the human face of the epidemics.


Detecting Prion Disease

"Mad cow" disease (bovine spongiform encephalopathy), its human counterpart variant Creutzfeld-Jakob disease (vCJD), and several other lethal neurodegenerative diseases are believed to be caused by misfolded prion proteins (PrP). Although prion diseases are rare in humans, there is concern about a potential epidemic and the recent reporting of three cases of vCJD transmitted by blood transfusion has underscored the importance of developing a reliable test to identify infected individuals before the appearance of clinical symptoms. Two Reports in the 7 Jul 2006 Science presented results from animal studies that could aid the development of prion disease diagnostics. Saá et al. ( http://www.sciencemag.org/cgi/content/short/313/5783/92 ) described how an in vitro amplification procedure allowed the biochemical detection of PrP in the blood of experimentally infected hamsters long before the animals showed signs of illness. The method could lead to the development of similar tests for human blood. Meanwhile, Trifilo et al. ( http://www.sciencemag.org/cgi/content/short/313/5783/94 ) examined scrapie infection in transgenic mice expressing a soluble form of PrP. The mice did not show neurological problems, but instead developed heart disease and high blood levels of the scrapie prion . Because the mouse model reliably produces infectious prions at detectable levels in the blood, it may be useful for determining the sensitivity of new diagnostic tests and treatments.


Bacterial Gold Miners

Prospectors panning streams for gold grains and nuggets owe thanks to tiny microbial helpers. According to a new Report by Reith et al. ( http://www.sciencemag.org/cgi/content/short/313/5784/233 ) in the 14 Jul 2006 Science , bacteria known to produce gold and other metals from solution in the laboratory also play a role in growing gold nuggets in nature. The team collected grains of so-called secondary gold from the soil of two mines in Australia . Upon close examination, they found that the grains looked like gold-encrusted bacteria and were overlain by bacterial biofilms. Genetic analysis of the biofilms revealed as many as 30 species of bacteria, most of which could not be found in the surrounding soil. The most pervasive species showed 99% similarity to Ralstonia metallidurans , a microbe known for growing in metal-rich environments and now shown to accumulate gold just inside their cell walls, or on their outer surface. The bacteria may precipitate toxic gold complexes as a way to detoxify their environment, but the details of exactly how they do this will require further investigation. An accompanying News story by R. A. Kerr ( http://www.sciencemag.org/cgi/content/short/313/5784/159a ) highlighted the Report.


Hands-On Meerkat Lessons

Although teaching is ubiquitous in human societies, there is little definitive evidence for teaching in other animals. Now, a study by Thornton and McAuliffe ( http://www.sciencemag.org/cgi/content/short/313/5784/227 ) in the 14 Jul 2006 Science reports that adult wild meerkats train younger meerkats to kill prey by opportunity teaching, in which they provide pupils with the chance to practice skills in an interactive process. Meerkats are small carnivorous mammals that belong to the mongoose family and eat a variety of fast prey including insects, lizards, and poisonous scorpions. Because young pups are incapable of finding their own food, and could be harmed by the more dangerous prey, adult "helper" meerkats kill or disable the prey for them. The researchers observed that as the pups grow older, the helpers modified their behavior, gradually introducing the pups to live prey, nudging prey towards them, and monitoring how they handled it. The helpers similarly modified their teaching behavior in response to played back recordings of the frequent high-pitched sounds of young pups or the lower, less repetitive sounds of more mature pups. As noted in an accompanying Science NOW story by M. Balter ( http://sciencenow.sciencemag.org/cgi/content/full/2006/713/2 ), this form of teaching need not require complex thinking such as awareness of the pupils' ignorance or deliberate intention to correct it.


Bee Declines in Europe

Many agricultural crops and natural plant communities depend on pollination by bees and other insects for reproduction. Now, a Report by Biesmeijer et al. ( http://www.sciencemag.org/cgi/content/short/313/5785/351 ) in the 21 Jul 2006 Science suggests that these pollination "services" are on the decline in some parts of the world. The team pored over nearly 1 million records of bee and hoverfly observations from national databases in Britain and the Netherlands . They divided the countries into 10 km by 10 km cells and then compared pollinator diversity before and after 1980. Their analysis revealed statistically significant declines in bee diversity across both countries, though hoverfly trends were more variable. Interestingly, bee and hoverfly specialists -- species that live in a narrow range of habitats or pollinate only a few species of plants -- have experienced greater relative declines than more generalist species. The team also found that plant species reliant on the declining pollinators have themselves declined relative to other plant species. As noted in an accompanying News story by E. Stokstad ( http://www.sciencemag.org/cgi/content/short/313/5785/286a ) these data suggest a causal link between pollinator and plant declines, but it is not clear which is driving the trend or if both are responding to some other factor. A co-author of the study discussed the possible causes and implications of the trends in a related podcast ( http://www.sciencemag.org/about/podcast.dtl#20060721 ).


Master Venom Defenders

Immune cells called mast cells help defend the body against certain bacteria and parasites, but these cells are best known for their role in triggering allergic attacks including asthma and anaphylactic shock. The inflammation-inducing molecules released by mast cells have also been thought to exacerbate the effects of venomous bites or stings. However, a Report by Metz et al. ( http://www.sciencemag.org/cgi/content/short/313/5786/526 ) in the 28 Jul 2006 Science now shows that mast cells can actually enhance resistance to toxic venoms. The team first tested the effects of venom from the Israeli mole viper on normal mice and on genetically engineered mast cell-deficient mice and found that it took 10 times as much venom to kill normal mice as the mice without mast cells. Further experiments showed that mast cells also protected mice from the more common western diamondback rattlesnake and southern copperhead, as well as from honeybee venom. The mast cells' protective effects seem to be due, at least in part, to their release of carboxypeptidase A, a protease that can break down the most dangerous component of several types of venom. As noted in an accompanying News story by J. Marx ( http://www.sciencemag.org/cgi/content/short/313/5786/427 ) it remains to be seen whether human mast cells share the same antivenom properties.


Third Way to Silence RNA?

The discovery of microRNAs and small interfering RNAs (siRNAs) has revolutionized our thinking about how gene expression is controlled. These two types of RNAs silence genes through distinct pathways that nevertheless share a number of components, including the endonuclease Dicer -- which produces RNAs with a characteristic length of about 22 nucleotides (nt) -- and two proteins of the Argonaute family that help form the ribonucleoprotein complexes that repress expression of target messenger RNAs. A flurry of recent papers, including two in the 21 Jul 2006 issue of Science now show that a third class of small RNAs, 29- to 30-nt in length, are involved in controlling gene expression in germline cells. Vagin et al. (published online 29 Jun; http://www.sciencemag.org/cgi/content/short/313/5785/320 ) reported that in the Drosophila germline, these RNAs -- called repeat-associated small interfering RNAs (rasiRNAs) -- ensure genomic stability by silencing so-called selfish genetic elements such as retrotransposons and repetitive sequences. Unlike siRNAs and miRNAs, rasiRNAs function through a subfamily of Argonaute proteins called Piwi and do not require Dicer. The RNAs are referred to as Piwi-interacting RNAs or piRNAs in mammals, and Lau et al. (published online 15 June; http://www.sciencemag.org/cgi/content/short/313/5785/363 ) characterized the piRNA complex (piRC) from rat testes. Both groups found that the piRNAs typically map to only one strand of genomic DNA, which suggests that in contrast to siRNAs and miRNAs, they do not arise from double-stranded precursors. As noted in an accompanying Perspective by R. W. Carthew ( http://www.sciencemag.org/cgi/content/short/313/5785/305 ), "further investigation should reveal how piRCs regulate the genome."


Musical Geometry

In Western music, two seemingly independent principles form the basis of composition: harmony and counterpoint. Harmony involves the selection of notes to create chords and the sequencing of those chords, whereas counterpoint is the art of connecting individual notes in a series of chords to form simultaneous melodies. The "rules" of harmony and counterpoint embody aesthetic norms but also represent constraints on the composer that can sometimes be difficult to reconcile. In a Report in the 7 Jul 2006 Science Tymoczko ( http://www.sciencemag.org/cgi/content/short/313/5783/72 ) showed that the relationships between harmony and counterpoint can be represented mathematically by mapping out the possible connections between chords in a topological space called an orbifold, in which points represent chords and line segments connecting them indicate how chords progress. Examination of the geometry of the orbifold can help our understanding of harmonic processes at work in musical compositions from Beethoven sonatas to jazz. It may even suggest new techniques to contemporary composers. An accompanying Perspective by J. Hook ( http://www.sciencemag.org/cgi/content/short/313/5783/49 ) discussed other mathematical approaches for exploring musical space. And Dr. Tymoczko, a composer and music theorist, talked about his work in the 7 Jul podcast ( http://www.sciencemag.org/about/podcast.dtl#20060707 ).


Rise of the Sierra Nevada

The Sierra Nevada Mountains in northern California stand about 2 kilometers above sea level, but when they arose has been widely debated. Now, clues from ancient raindrops suggest that the range has been standing tall for some 50 million years. In a study reported in the 7 Jul 2006 Science , Mulch et al. ( http://www.sciencemag.org/cgi/content/short/313/5783/87 ) analyzed the hydrogen isotope composition of clay minerals in prehistoric Sierra river sediments, which have incorporated water from precipitation over time. Importantly, precipitation has different ratios of hydrogen isotopes depending on the altitude of the clouds when it fell. Deuterium, for example, is a slightly heavier form of hydrogen and tends to fall at low elevations when a cloud first encounters a mountain. As a cloud climbs the mountain, rainwater become lighter, and the ratios of heavier to lighter isotopes grows smaller. The researchers found that the isotopic composition in the ancient sediments was very similar to the composition of recent precipitation, which implies that the mountains have been high since about 40 to 50 million years ago.. This result is at odds with the competing hypothesis that the mountains rose from sea level just 3 to 5 million years ago after a large chunk of Earth's crust broke off and fell into the mantle. A Science NOW story by B. Mason ( http://sciencenow.sciencemag.org/cgi/content/full/2006/706/3 ) published on 6 Jul highlighted the study.


Supernova Dust Factories

Interstellar dust, consisting largely of carbon and silicate grains, is prevalent in the universe and plays an important role in regulating its thermal energy balance, catalyzing chemical reactions in molecular clouds, and in providing the basic building blocks for a variety of objects in the solar system. But where did the dust come from? It has been suggested that supernova explosions are responsible for spreading the dust from the dying embers of stars, but scientists have failed to find enough dust in supernovae to support this idea. . .until now. In a study reported in the 14 Jul 2006 Science (published online 8 Jun), Sugerman et al. ( http://www.sciencemag.org/cgi/content/short/313/5784/196 ) used the Spitzer Space Telescope to map the infrared glow from warm dust around the recent supernova 2003gd. Observable signatures in the supernova's optical and infrared spectrum indicate that dust began forming as early as 250 days after the outburst. And over some 680 days, the supernova produced 10 times more dust than has been seen after any such stellar explosion. If other supernovae produced similar quantities of dust, these explosions could have been the dominant dust factories in the early universe. An accompanying Perspective by E. Dwek ( http://www.sciencemag.org/cgi/content/short/313/5784/178 ) highlighted the study.


Explaining Glacial Cycles

The episodic nature of Earth's glacial and interglacial periods is believed to be caused by long-term changes in the amount of energy Earth receives from the Sun (insolation) and in seasonal variations driven by three major cycles: a 100,000-year eccentricity cycle (regular changes in the Earth's orbit around the sun), a 41,000-yr obliquity cycle (oscillations in the tilt of Earth's axis), and a 23,000-year precession cycle (changes in the direction of Earth's axis of rotation). Curiously, Earth's glacial oscillations between 3 and 1 millions years ago have followed a 41,000-year cycle when the 20,000-year precessional effects should have been stronger. Two studies in the 28 Jul 2006 Science (published online 22 Jun) offered two new explanations for this paradox. Raymo et al. ( http://www.sciencemag.org/cgi/content/short/313/5786/492 ) argue that the early glacial cycles appear to have a 40,000-year cycle because the opposing 23,000-year insolation cycles in the Northern and Southern hemispheres may have canceled one another. Huybers ( http://www.sciencemag.org/cgi/content/short/313/5786/508 ), on the other hand, maintain that ice age models have been incorrectly using peak summer insolation to estimate ice mass variability, when they should have instead used the integrated amount of solar energy received over the duration of the summer. An accompanying Perspective by D. Paillard ( http://www.sciencemag.org/cgi/content/short/313/5786/455 ) lent historical context to these new arguments.


Golden Amine Synthesis

Aromatic amines are organic compounds that constitute important intermediates for the manufacture of pharmaceuticals, pigments, dyes, and herbicides. They are produced by reducing corresponding nitro compounds, but many of the methods that can reduce the nitro group without reducing other groups in the molecule produce environmentally unfriendly byproducts or have low yields. In a Report in the 21 Jul 2006 Science , Corma and Serna ( http://www.sciencemag.org/cgi/content/short/313/5785/332 ) showed that gold nanoparticle catalysts supported on titanium or iron oxides can selectively reduce the nitro groups of an aromatic nitro compound while leaving the rest of the molecule intact. Moreover, the catalysts work under mild reaction conditions and create few unwanted byproducts. As noted in an accompanying Perspective by H.-U. Blaser ( http://www.sciencemag.org/cgi/content/short/313/5785/312 ), "[t]he scope of the new catalysts and their mode of action remain to be established, but the promising results should give a strong stimulus to this area of catalytic chemistry."


In Science's STKE

Rule-Based Signaling Models

Many diseases are caused by molecular changes that affect signal-transduction systems. Thus, in addition to our curiosity about the mechanisms that cells use to respond to signals, there is practical motivation to better understand the processes of cellular signaling. Mathematical models have helped researchers gain a quantitative and predictive understanding of the functional roles of proteins and the effects of modifying protein interactions in a particular system. But current models often fail to account for the complexities of these interactions, which include innumerable posttranslational modifications and the formation of protein complexes. In a Review published 18 Jul 2006 in Science 's Signal Transduction Knowledge Environment (STKE), Hlavacek et al. ( http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2006/344/re6 ) discussed new modeling approaches that cope with such complexity by specifying protein-protein interactions as rules that serve as generators of chemical reactions (or reaction events) and chemical species. A rule specifies the features of proteins that are required for or affected by a particular protein-protein interaction. The authors discussed applications of the approach, issues that arise in model specification and testing, and several of the specific software tools available for rule-based modeling.

Also in STKE this month:
--Gao and Bromberg discussed the role of the transcription factor STAT 3 in cell migration ( 11 Jul 2006 ; http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2006/343/pe30 )
--Kenakin highlighted the therapeutic potential of G protein-coupled receptors ( 3 Jul 2006 ; http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2006/342/pe29 )
--Swamy et al. presented a protocol for blue native polyacrylamide gel electrophoresis, which allows for the identification and analysis of multiprotein complexes ( 25 Jul 2006 ; http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2006/345/pl4 ).