Science Roundup

This month in Science Roundup:

Genetics of Behavior
Bad Behavior Spreads
Insights into RT Versatility
Native or Not?
Understanding Leukemic Relapse
Fat Metabolism and Longevity
Homo erectus Hips
Views of Extrasolar Planets
Climate, Sun, and Culture
Explaining Mantle Conductivity
Probing Molecular Dynamics
In Science Signaling

This month’s Science Roundup is sponsored by: Science Careers

New Science Careers Webinar: State of the Nation: Science in Ireland – December 10, 2008, at 11 a.m. Eastern Time (8 a.m. Pacific, 4 p.m. GMT)

In recent years Ireland has made significant progress in building its scientific research capacity. Recently, the Irish government set down a bold vision to build a "knowledge economy." Join us for a roundtable discussion that will look at what policy decisions have been taken to deliver on this vision, consider the progress made to date and the funding and research opportunities in industry and academia in Ireland, as well as examine the challenges encountered. Questions can be asked live!

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Genetics of Behavior
Introduction to Special Issue

Genes do not specify behavior directly, but rather encode proteins that build and govern the complex neural circuits through which behavior is expressed. Identifying how genetic variation modifies these circuits, however, can help us understand both how and where behavior is initiated. A special section of the 7 Nov 2008 Science explored what genetic and genomic approaches have taught us about behavior in species from bees to humans. An opening News story looked at a handful of genes that have recently been linked to variations in human temperament and personality. Review articles examined the complex relations between genes, the brain, and social behavior (with related podcast interview); the role of the neuropeptides oxytocin and vasopressin in modulating social cognition and reproductive behaviors across species; and the neurobiology of fruit fly mating decisions. And two Perspectives looked at the influence of genetics on human political behavior and how the methods used to understand the molecular basis of circadian rhythms can be applied to other behaviors such as addiction and learning.

Bad Behavior Spreads

If you are walking through a litter-strewn park, are you more likely to litter? The idea that signs of disorderly or petty criminal behavior trigger more or other types of disorderly and criminal behavior is known as the broken window theory; it forms the backbone of many major cities’ crime prevention efforts, yet still lacks robust empirical support. In a Report published online in ScienceExpress on 20 Nov 2008, Keizer et al. described a series of clever field experiments conducted in the Netherlands designed to address the effects of disorder in the environment on people’s behavior. The team found that when people observe that others have violated a certain social norm or legitimate rule, they are more likely to violate other norms or rules, which causes disorder to spread. For example, people were much more likely to litter a graffiti-adorned alley than one in which the walls were clean or to steal money from a littered area versus a clean one. Even the sound of illegal fireworks caused people to litter more so than when it was quiet. The authors note that their findings present a clear message to policymakers and police enforcement: that early disorder diagnosis and intervention are of vital importance when fighting the spread of disorderly activity. An accompanying News story by C. Holden highlighted the study.

Insights into RT Versatility

For HIV to replicate inside human cells, it must convert its single-stranded RNA genome into double-stranded DNA that can be integrated into the host genome. This complex process requires several enzymatic activities, including DNA synthesis, degradation of the RNA strand of the RNA-DNA replication intermediate, strand displacement to remove the remaining RNA and DNA fragments to allow synthesis of the second DNA strand, and strand transfer to move newly synthesized DNA within or between templates. Remarkably, all of these tasks are carried out by a single enzyme: HIV reverse transcriptase (RT). In a Report in the 14 Nov 2008 Science, Liu et al. offered new insight into how RT switches between its multiple functions. Using fluorescence resonance energy transfer, the team monitored the interactions of individual RT molecules with nucleic acid substrates in real time. They found that the enzyme slides over long distances on nucleic acid duplexes, rapidly shuttling between opposite ends. In addition, it can spontaneously flip between opposite binding orientations that support different enzymatic activities. As RT is a major target for anti-HIV therapies, a greater understanding of this enzyme could aid future drug design. An accompanying Perspective by S. G. Sarafianos and E. Arnold highlighted the Report.

Native or Not?

The Galápagos Islands are home to an exceptional array of fauna and flora, including some 500 native flowering plants and ferns. Although 95% of the islands’ biological diversity is still intact, extinction rates are among the highest in the world. Invasive plants that transform habitat are particularly worrisome because they can disrupt conditions that are necessary for a native species’ survival; the removal of nonnative species has thus become a key conservation-restoration priority. A new study reported in the 21 Nov 2008 Science underscored the fundamental importance of distinguishing whether a species is native or has been introduced before such restoration efforts are undertaken. Van Leeuwen et al. studied fossil pollen and plant remains preserved in sedimentary deposits -- dating as far back as 8200 years ago -- collected from Santa Cruz Island in the center of the Galápagos archipelago. The team found that six species presumed to be introduced or doubtfully native by at least one of the Galápagos botanical authorities are in fact native to the islands, and were present thousands of years before human colonization (see the related ScienceNOW story by E. Pennisi). Corresponding author Cynthia Froyd discussed the implications of these findings for conservation efforts in the Galápagos and other oceanic islands in a related podcast interview.

Understanding Leukemic Relapse

Acute lymphoblastic leukemia (ALL) is the most common leukemia in children. Most children are cured of the disease after treatment, but the survival rate of those who experience relapse after treatment is poor. Although biological and clinical differences have been identified between diagnostic and relapsed leukemic cells, many questions remain about the molecular abnormalities responsible for relapse, as well as the relationship between the cells giving rise to the primary and recurrent leukemias in individual patients. In a Report in the 28 Nov 2008 Science, Mullighan et al. investigated the cellular and genetic origins of ALL relapse by performing genome-wide DNA copy number analyses on matched diagnostic and relapse bone marrow samples from 60 children with the disease. The team found that the diagnosis and relapse samples typically showed different patterns of copy number abnormalities. In particular, most relapse samples lacked some of the alterations present at diagnosis, which suggests that the cells responsible for relapse are ancestral to the primary leukemia cells. In addition, the genomic alterations acquired at relapse preferentially affected genes implicated in cell cycle regulation and B cell development, suggesting that these functions might be appropriate targets for new therapies for relapse patients. First author Charles Mullighan and senior author James Downing discussed the study in a related podcast interview.

Fat Metabolism and Longevity

According to a new study in the 7 Nov 2008 Science, burning fat leads to longer life -- at least in worms. Although previous studies have demonstrated a positive correlation between lifespan and dietary restriction, the mechanisms that couple fat storage, lifespan, and reproduction remain poorly understood. In their Report, Wang et al. found that activation of a fat-burning enzyme in the roundworm Caenorhabditis elegans decreases fat storage and leads to leaner and longer-lived worms. The level of the enzyme -- a triglyceride lipase called K04A8.5 -- is low during adulthood, but increases markedly when germline stem cells (which give rise to male and female reproductive cells) stop proliferating. This enzyme up-regulation causes increased lipid hydrolysis and prolongs life span: Worms with the lipase over-expressed in fat storage tissue lived 24% longer than control animals. The lipase also contributes to the increase in worm longevity induced by decreased insulin signaling. An accompanying Perspective by T. Xie highlighted the Report.

Homo erectus Hips

The modern human pelvis is uniquely modified to accommodate both bipedal locomotion and the birthing of large-brained offspring. Despite the importance of hip morphology to human body shape and development, researchers’ understanding of human hip evolution has been limited. That is because sufficiently preserved pelvic bones are very rare in the fossil record. In a Report in the 14 Nov 2008 Science, Simpson et al. described a nearly complete early Pleistocene adult female Homo erectus pelvis recovered from Gona, Ethiopia, dated to ~0.9 to 1.4 million years ago. Previous estimates of female H. erectus birth canal dimensions -- based on pelvis fragments from a juvenile male skeleton -- indicated that H. erectus pelves were restricted to birthing small-brained babies. Analysis of the new female fossil, however, reveals an "obstetrically capacious" pelvic opening that could have allowed a neonate brain size up to 30% larger than earlier estimates. Moreover, the team surmises that H. erectus did not have the tall, narrow body form of modern humans adapted to tropical, semi-arid environments or hips adapted for long distance running, previously thought to characterize H. erectus. A related News Focus by A. Gibbons explored what morphological analyses of this and other fossil hominids can tell us about the prenatal growth of our ancestors and the evolution of childhood.

Views of Extrasolar Planets

More than 300 planets have been found outside the solar system, most of them discovered indirectly through their influence on their parent star. In the 28 Nov 2008 Science two groups presented the first direct observations of the infrared and optical signatures of planets orbiting distant stars that resemble our Sun. Kalas et al. (published online 13 Nov) presented Hubble Space Telescope images of a planet with a mass no more than three times that of Jupiter orbiting the star Fomalhaut, 25 light years from Earth. Marois et al. (also published online 13 Nov) presented near-infrared images captured by the Keck and Gemini telescopes of three giant planets orbiting a star 128 light years from Earth in the constellation Pegasus. In a podcast interview, lead author Christian Marois noted that this latter system resembles a scaled-up version of the outer portion of our solar system, with the planets’ masses estimated to be between 5 and 13 times that of Jupiter. Both extrasolar systems are similar in that dusty debris disks surround the primary stars, both of which are younger, brighter, warmer, and more massive than the Sun. An accompanying Perspective by M. S. Marley highlighted the new observations.

Climate, Sun, and Culture

The Asian Monsoon transports large amounts of heat and moisture from the ocean to the most-populated regions of the world, and as such, plays in important role in climate. Now, in a Report in the 7 Nov 2008 Science, Zhang et al. have used isotopic data derived from stalagmites from Wanxiang Cave, China to reconstruct a detailed history of the Asian Monsoon over the past 1810 years. The new record reveals connections between the monsoon’s strength, solar irradiation, Northern Hemispheric temperature, and glacial cycles in Europe. Comparing their rain record with Chinese historical records, the team also found that three of the five multicentury dynasties during that time -- the Tang, the Yuan, and the Ming -- ended after several decades of abruptly weaker and drier summer monsoons, possible poor rice harvests, and social unrest. In contrast, the decades that included the strongest and wettest monsoons coincide with the beginning of the Northern Song Dynasty, a period of increased rice cultivation, dramatic population rise, and social stability. An accompanying News story by R. A. Kerr noted that the cave record "provides the strongest evidence yet for a link among sun, climate, and culture."

Explaining Mantle Conductivity

Earth’s rocky mantle extends from roughly 40 kilometers to 2900 kilometers beneath the surface -- between the bottom of the crust and the planet’s molten core. Some regions of the mantle and deep crust have curiously high electrical conductivities, which have been interpreted to reflect the presence of either silicate melt or water dissolved in olivine. In a Report in the 28 Nov 2008 Science, Gaillard et al. presented an alternative explanation. Using laboratory measurements, the team showed that the electrical conductivities of molten carbonate minerals -- the kind that would be produced at depths of ~200 to 300 km -- are three orders of magnitude higher than those of molten silicate and five orders of magnitude higher than those of hydrated olivine. Thus, small amounts of carbonate melt could be present in the mantle. The team further showed that the high conductivity of the mantle beneath the ocean crust could be explained if 0.1% of the mantle volume consisted of carbonate melt, a number that is consistent with the carbon dioxide content of mid-ocean ridge basalts. An accompanying Perspective by R. L. Evans discussed the competing models of mantle electrical conductivity.

Probing Molecular Dynamics

A strong oscillating laser field can pull electrons from the outer layer of an atom or molecule and then send them careening back, releasing high-energy photons upon collision. This process is known as high harmonic generation (HHG). By monitoring the oscillating x-ray emissions resulting from the collisions in a vibrating molecule, dynamic changes in the molecule’s electronic configuration can be monitored in real time. Two studies in the 21 Nov 2008 Science have done just this. Li et al. used high harmonics to interrogate the electronic dynamics in dinitrogen tetraoxide and found that electrons can be ejected from multiple orbitals of the molecule by exploiting different stages in its excited vibrations. McFarland et al. probed molecular nitrogen and found distinct spectral signatures depending on the spatial orientation of the nitrogen molecules relative to the polarization of the applied laser field. According to an accompanying Perspective by G. Doumy and L. F. DiMauro, the new studies "show how it is possible to use HHG selectively for probing different molecular orbitals, thus meeting a necessary condition for studying the internal dynamics of complex molecular systems."

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In Science Signaling

Focus on TGF-beta

The transforming growth factor-beta (TGF-beta) superfamily is a large family of extracellular ligands involved in regulating many biological processes including development, wound healing, and cell proliferation and survival. Because these proteins can have both growth-promoting and growth-inhibiting effects, they have been implicated both in tumorigenesis and metastasis and in preventing these pathological phenotypes. A special focus issue of Science Signaling published on 18 Nov 2008, highlighted recent insights into the regulation of TGF-beta signaling and points of intersection of this pathway with other signaling pathways. A Perspective by L. L. Hoover and S. W. Kubalak discussed the noncanonical roles of Smad proteins, which were originally identified as key transducers of TGF-beta signals. Another Perspective by F. Liu discussed recent work identifying PCTA as a regulator of TGF-beta signaling. This protein promotes TGF-beta-mediated transcriptional regulation and growth inhibition. Finally, in the Open Forum on Cell Signaling, N. R. Gough reported on a recent one-day symposium that presented interesting new facets of TGF-beta signaling as well as a historical perspective on how this molecule and its family members have contributed to the concept of context-dependent signaling and advanced our understanding of diseases such as cancer.

-- Zurhove et al. showed that cleavage of the intracellular domain of the lipoprotein receptor LRP1 allows it to transcriptionally inhibit inflammatory responses (25 Nov 2008)
-- M. B. Major et al. identified new regulators of Wnt/beta-catenin signaling by integrative molecular screening (11 Nov 2008)
-- A. H. Guse and H. C Lee reviewed recent advances in our understanding of calcium signaling mediated by nicotinic acid adenine dinucleotide phosphate or NAADP (4 Nov 2008)