Science Roundup


This month in Science Roundup:


Cancer Crusade at 40
Special Online Collection

In 1971, the U.S. National Cancer Act became law -- thereby providing a massive stimulus for cancer research. Now, 40 years later, many research and treatment questions that then vexed the cancer community remain unanswered. Yet the "cancer crusade" of the last four decades has unquestionably changed therapies and saved lives. In a special section in its 25 Mar 2011 issue, Science and its companion journals and Web sites commemorate the campaign's 40th anniversary with a look at the state of cancer science today. A special news section explores the achievements (and shortfalls) of the past 40 years, targeted-drug therapies and other treatment research, the dilemmas posed by rising treatment costs, and efforts to fight cancer in the developing world. Review articles by leading cancer researchers look at the state of cancer genomics, the enigmatic phenomenon of metastasis, and the new research framework of "cancer immunoediting." A related video and special cancer edition of the Science Podcast feature interviews with authors and cancer scientists. In Science Signaling, a full issue focuses on the pathways that mediate drug resistance -- a key to developing new cancer therapies. And Science Translational Medicine likewise devotes a full issue to cancer themes, including commentaries on cancer clinical trials, research on aspects of breast and lung cancer, and a podcast. Also: Science Careers features several stories on building a career in cancer research.


Afghanistan: Counting the Dead
Special Online Collection

As the war in Afghanistan -- the longest in U.S. history -- grinds toward the decade mark, the sometimes murky and divergent accounting for the war's cost in civilian casualties has complicated assessments of progress. The deluge of raw (and classified) data from WikiLeaks during 2010 brought the civilian-casualties issue to the front burner, but included many uncertainties that have made the data difficult to interpret. Early this year, however, the U.S. military provided Science with its internal record of the death and injury of Afghan civilians -- the "CIVCAS" data set -- for public release, and the United Nations and the Kabul-based Afghanistan Rights Monitor offered versions of their own casualty data sets for similar release. Science assembled a team of experts to analyze the data, and in a special News Focus on 11 Mar 2011, contributing correspondent John Bohannon detailed both the analysis and the backstory of the CIVCAS data's release. Based on the expert analysis, the data suggest that the war has become more lethal to the Afghan population over time. But while the total number of civilian casualties is increasing, the data indicate that the military has adapted, causing a shrinking share of the death and injuries in spite of last year’s surge in troops and combat operations. Improvised explosive devices continue to be the number one killer in the country. Also online: The data release itself, a podcast interview with Bohannon, and a special interactive visualization of the data created by G. M. Brower.


Exploiting Ancient Seas

By about 13,000 years ago, Paleoindians had spread through the North American interior, but little is known about their settlement, economies, and technologies along the coast. In a Report in the 4 Mar 2011 Science, Erlandson et al. described archaeological sites on California’s Channel Islands that provide evidence for seafaring and island colonization by Paleoindians with a diversified maritime economy about 12,000 years ago (listen to the podcast interview with one of the study's authors, Torben Rick). The sites contain stemmed points, crescents, and other stone tools that resemble artifacts from numerous sites associated with glacial lakes in the western North American interior. A variety of faunal remains associated with the artifacts suggest that these the sites served as hunting grounds for marine birds, mammals, shellfish, and fish.  At that time, the islands were still several kilometers offshore, requiring boat travel to reach them. A related News story by M. Balter considered how the new finds fit with the so-called "coastal hypothesis", which posits that prehistoric peoples, once they arrived in Alaska via a land bridge from Asia, journeyed by boat down the coast of North America rather than through the continent's interior.


Peeling Graphene

Graphene, a sheet of carbon atoms just one atom thick, is the thinnest known material and the strongest measured -- and its exceptional electronic properties have attracted the attention of physicists, chemists, and computer-chip-device makers. Graphene's properties can vary as a function the number of carbon layers in a sample. However, existing methods for etching the types of patterns useful for fabricating electronic devices do not allow control of the number of graphene layers that can be removed. Now, in a Report in the 4 Mar 2011 Science, Dimiev et al. describe a chemical route for the layer-by-layer removal of graphene from various types of graphene materials ( listen to the related podcast interview with senior author James Tour). Their method involves coating graphene with a thin layer of zinc -- which can be patterned on the surface -- and then dissolving it with dilute hydrochloric acid, which removes one graphene layer and leaves the lower layers intact. The technique helps pave the way for the design of graphene-based electronics that promise to be smaller, faster, and more energy-efficient than conventional silicon-based devices. An accompanying Perspective by D. Gunlycke and P.E. Sheehan highlighted the Report.


Made to Move

Among the most fascinating cellular enzymes are molecular motors, which elegantly couple adenosine triphosphate (ATP) hydrolysis to directional mechanical motion. Dynein is a large cytoskeletal motor protein that moves along microtubules to power such functions as the beating of cilia and the transport of intracellular cargo. Evolved from the so-called AAA ATPases -- a family of ring-shaped ATP-hydrolyzing enzymes that participate in a variety of cellular functions -- dynein has a size and complexity that have posed challenges for understanding its structure and mechanism. Now, in a Research Article in the 4 Mar 2011 (published online 17 Feb) Science, Carter et al. present the 6-angstrom crystal structure of a dimer of two ~300-kilodalton motor domains of yeast cytoplasmic dynein. The structure suggests how conformational changes in the ring associated with ATP binding and hydrolysis might be relayed through the protein's microtubule-binding "stalk" structure, leading to a model for the mechanism of motility. A Perspective by J.A. Spudich highlighted the study.


Prehistoric Social Networking

A hunter-gatherer life-style is thought to have been the predominant social structure for most of human history. The common assumption is that hunter-gatherer groups consisted largely of related individuals: parents, siblings, and offspring, possibly extending to include spousal relations. In a Research Article in the 11 Mar 2011 Science, Hill et al. analyzed the kin relationships of groups in 32 contemporary hunter-gatherer societies and found that these societies display a social structure different from any other primate or vertebrate (listen to the related podcast interview with lead author Kim Hill). Although adult brothers and sisters often co-reside, most individuals in residential groups are genetically unrelated. In addition, both sexes alike can choose to leave their group or to stay, and neither the maternal lineage nor the paternal lineage is dominant within a group. These patterns produce large interaction networks of unrelated adults and suggest that inclusive fitness cannot explain extensive cooperation in hunter-gatherer bands. However, large social networks may help to explain why humans evolved capacities for social learning that resulted in cumulative culture. An accompanying Perspective by B. Chapais considered how the unique multigroup structure of human societies may have originated.


Aerosol Lessons from Deepwater

In Earth's atmosphere, aerosol particles scatter incoming solar radiation and act as sites for condensation of water during cloud formation. Human activities can alter this population of particles, thereby affecting climate and air quality, but our inability to accurately predict the composition and mass of atmospheric aerosols, is inhibiting progress in both areas. A Report in the 11 Mar 2011 Science offered new insights into the formation of a large fraction of atmospheric aerosols, volatile organic compounds -- insights made possible by a recent environmental disaster: the Deepwater Horizon oil spill in the Gulf of Mexico. deGouw et al. took airborne measurements of the gaseous and aerosol composition of the air above the spill and identified a narrow plume of hydrocarbons downwind of the spill site, which they attribute to the evaporation of fresh oil on the sea surface. They also detected a wider plume with high concentrations of organic aerosols that appear to be "secondary" aerosols, formed from unmeasured, less volatile hydrocarbons that spread over a wider area because they took longer to evaporate. As noted in an accompanying Perspective by H. Coe, the work indicates that "the organic compounds responsible for particle formation are not the same compounds that control ozone formation, which are generally of higher volatility," and that this result could influence the future regulation of ozone and particulates.


Tortoise vs. Hare: E. coli Edition

What really determines evolutionary success -- an organism's immediate fitness, or its ability to continue to adapt steadily over time? In a Report in the 18 Mar 2011 Science, Woods et al. provided new insight on that question, by "replaying the evolutionary tape" multiple times with a bacterial population. The team revived a frozen population of E. coli from a long-term evolution experiment, and compared the fitness -- and ultimate outcomes -- of four genetically distinct clones in multiple runs of the evolutionary race. The long-term winners turned out not to be the two clones that mutated and evolved rapidly, and thus had higher immediate competitive fitness, but the more slowly mutating clones that would seem to have lower competitive fitness. The reason, the researchers suggest, is that eventual winners had better "evolvability" -- that is, greater potential for further adaptation over the long haul. The rapidly mutating losers, by contrast, quickly gained superior fitness in the short run, but also appear to have picked up mutations that closed off future pathways for further adaptation -- thereby providing an opening for the slower-mutating clones to take over the entire colony. Senior authors Jeffrey Barrick and Richard Lenski discussed the work in a related podcast segment.


Help for Heart Failure?

Systolic heart failure -- the disease's most common manifestation -- occurs when contractions of the heart's ventricle muscle wall are weakened to the point that they fail to pump blood out of the heart and into the larger circulatory system. Existing therapies to treat systolic heart failure rely on tweaking signaling pathways tied to cardiac contractility, an indirect approach that carries a number of potentially fatal side effects. Now, research published in Science proposes an alternative course: using a previously discovered small molecule that directly beefs up the function of cardiac myosin, the motor protein that powers heart contractions. In a study in the 18 Mar 2011 issue, Malik et al. demonstrated that a drug based on the small molecule omecamtiv mercabil was effective in increasing cardiac function in dogs and rodents, both those with healthy hearts and those with symptoms of heart failure. According to Malik et al., the molecule apparently works by binding to a specific site on the myosin molecules and causing changes that increase the rate of ATP turnover -- thereby ultimately accelerating the transition of the myosin molecules to their force-producing state. As noted in a related Perspective by L. A. Leinwand and R. L. Moss, a key advantage is that the small molecule directly targets a subset of myosins that are expressed only in a limited set of tissues. That characteristic should reduce the kinds of side effects that have plagued existing, indirect therapies.


Ice Sheets: Growing from Below

Large ice sheets, like the one covering Antarctica, grow over millennia as snow accumulates, compresses, and crystallizes faster than it disappears. That simple view forms a core assumption for models of ice sheet dynamics, and a guidepost in the ongoing search for the oldest ice on Earth. But the story may not be quite so simple. In a paper in Science on 25 Mar 2011 (published online 3 Mar 2011), Bell et al. document the apparent presence, in parts of the East Antarctic ice sheet, of substantial thicknesses of ice that did not fall as snow from above, but were frozen from below onto the sheet's basal layer. Using a variety of airborne and ground-based techniques including improved ice-penetrating radar, the team imaged the ice sheet's internal structure in several cross-sections, and found patterns of internal reflections consistent with pockets of ice frozen on from below -- with the freeze-on in some cases accounting for as much as half of the sheet's total thickness. The finding, as noted in an accompanying Perspective by S. Tulaczyk and S. Hossainzadeh, points to the existence of an internal hydrological system that redistributes mass and heat within the ice sheet, and will necessitate new models of subglacial water generation, flow, and freezing to better establish the potential effects of climate change on ice sheet movement -- and to aid the search for Earth's oldest ice.

In Science Signaling

T Cells Lose Their Identity

Regulatory T cells (Tregs) inhibit the actions of inflammatory T cells during immune responses, and they prevent autoimmunity. In the 1 Mar 2011 issue of Science Signaling, Schenk et al. showed that ATP signaling through purinergic receptors on Tregs inhibited their immunosuppressive effects and exacerbated tissue inflammation in mice. Worse still, ATP signaling made the Tregs lose their identity and induced their conversion into pro-inflammatory cells. These data suggest that ATP signaling through purinergic receptors might be an effective therapeutic target to counteract unwanted and deleterious inflammation.

Also in Science Signaling this month:
-- Sasaki et al. found that blocking ubiquitination of K-Ras may be a potential strategy for targeting some cancers, and Pfleger discussed this research in the context of the effects of ubiquitination of different Ras isoforms (8 Mar 2011).
-- Liang et al. engineered a system for controlling protein activity and localization in mammalian cells using components of a plant hormone signaling pathway (15 Mar 2011).
-- Lau et al. performed a systems-level analysis of the intestinal response to the inflammatory cytokine TNF-α, which yielded results with implications for treating inflammatory bowel disease (22 Mar 2011).


In Science Translational Medicine

Nanodiamonds are Forever

Nanodiamonds -- tiny carbon particles -- are biocompatible, can be scalably synthesized, and can bind therapeutic agents, which makes them a promising platform for drug delivery. In the 9 Mar 2011 issue of Science Translational Medicine, Chow et al. report that binding nanodiamonds to the anticancer drug doxorubicin (Dox) improved therapeutic response and overcame chemoresistance in mouse models of mammary and liver cancer. Believed to act by interfering with DNA synthesis, Dox is commonly used to treat a wide variety of cancers; however, many cancers become resistant to Dox during treatment, in part because of the drug's efflux from the tumor cells. Chow et al. conjugated Dox to nanodiamonds as a possible means of preventing the drug from being pumped out of cells. Indeed, the nanodiamond-Dox complexes were retained better by cancer cells, decreased tumor growth, and displayed less toxicity when compared with unconjugated Dox. The gradual release of Dox from the nanodiamonds allowed for enhanced tumor retention and efficacy, but the small size allowed for clearance before toxicity occurred in slower-dividing healthy tissues. The potential of using nanodiamonds to overcome drug resistance during cancer chemotherapy is discussed by T. Merkel and J.M. DeSimone in a related Perspective.

Also in Science Transational Medicine this month:
-- Ateeq et al. showed that SPINK1 is a new extracellular therapeutic target for a subset of patients with prostate cancer (also see the Perspective by Goldstein et al.) (2 Mar 2011)
-- Lande et al. and Garcia-Romo et al. demonstrated a role for neutrophils and "neutrophil extracellular traps," a specialized structure that neutrophils release when activated, in the pathogenesis of systemic lupus erythematosus (also see the Perspective by J. Craft) (9 Mar 2011)
-- Burington et al. found that a 15-gene expression signature predicts whether a patient with diffuse large B cell lymphoma will respond to dacetuzumab, a therapeutic antibody (16 Mar 2011)
-- Fang et al. reported that breast cancer methylomes contribute to metastatic potential, modulate the metastasis transcriptome, and predict disease outcome; senior author T. Chan discussed the findings in a related podcast (23 Mar 2011)


Image credits (in order of appearance): Anne Weston, Cancer Research UK, Visuals Unlimited, Inc.; University of Oregon; Daniel Lack, courtesy of CIRES and NOAA; Robin E. Bell/Lamont Doherty Earth Observatory of Columbia University