Alkenes constitute a large fraction of the natural and human-made volatile organic compounds (VOCs) that are emitted into the troposphere. Their oxidation products degrade air quality and contribute to climate warming. Alkene oxidation is thought to involve Criegee intermediates (CIs), highly reactive molecules that form when ozone reacts with alkenes. However, the impact of CIs may be limited if they react rapidly with water. Modelers have found it difficult to quantify the effect of CIs on atmospheric composition, because laboratory data on CI reactions with water have been contradictory. On page 751 of this issue, Chao et al. (1) show that the simplest CI, formaldehyde oxide (CH2OO), reacts rapidly with the water dimer, (H2O)2. Similar results are reported by Lewis et al. (2). Author: Mitchio Okumura

Elucidating catalytic reaction mechanisms is often a challenge, and these difficulties are compounded in the case of enantioselective catalysts. The ability of a catalyst to preferentially form one enantiomer over the other often hinges on the balance of many attractive and repulsive nonbonded interactions that occur in competing transition states. On page 737 of this issue, Milo et al. (1) combine physical organic and computational quantum chemistry with modern data analysis techniques to identify these interactions. Their predictive mathematical models elucidate the underlying reaction mechanism and the role of nonbonded interactions in these enantioselective reactions, facilitating the rational design of more effective catalysts. Authors: Tongxiang Lu, Steven E. Wheeler

The medical profession has long recognized the importance of randomized evaluations; such designs are commonly used to evaluate the safety and efficacy of medical innovations such as drugs and devices. Unfortunately, innovations in how health care is delivered (e.g., health insurance structures, interventions to encourage the use of appropriate care, and care coordination approaches) are rarely evaluated using randomization. We consider barriers to conducting randomized trials in this setting and suggest ways for overcoming them. Randomized evaluations of fundamental issues in health care policy and delivery should be—and can be—closer to the norm than the exception. Authors: Amy Finkelstein, Sarah Taubman

Plants behave on their own time scale, with their own unique physiology, and according to author and plant physiologist Anthony Trewavas, solve problems equally as complex as those confronting humans. But are animal and plant behaviors really comparable? And are plants truly "intelligent"?  Behavioral ecologist Andrew G. Zink and plant physiologist Zheng-Hui He consider the advantages and disadvantages of applying animal-centric analogies to plants in a review of Plant Behaviour and Intelligence. Authors: Andrew G. Zink, Zheng-Hui He

The dramatic stories behind the discovery of the heart's role in our physiology, and the ways we now treat its many maladies, feature improbable heroes and daring experiments. Physician Yevgeniya Nusinovich explores a history of our understanding of the heart in a review of The Man Who Touched His Own Heart: True Tales of Science, Surgery, and Mystery. Author: Yevgeniya Nusinovich

Authors: Nicholas A. Ashford, Patricia Bauman, Halina S. Brown, Richard W. Clapp, Adam M. Finkel, David Gee, Dale B. Hattis, Marco Martuzzi, Annie J. Sasco, Jennifer B. Sass

Banks-Leite et al. (Reports, 29 August 2014, p. 1041) conclude that a large-scale program to restore the Brazilian Atlantic Forest using payments for environmental services (PES) is economically feasible. They do not analyze transaction costs, which are quantified infrequently and incompletely in the literature. Transaction costs can exceed 20% of total project costs and should be included in future research. Author: Christopher Finney

Finney claims that we did not include transaction costs while assessing the economic costs of a set-aside program in Brazil and that accounting for them could potentially render large payments for environmental services (PES) projects unfeasible. We agree with the need for a better understanding of transaction costs but provide evidence that they do not alter the feasibility of the set-aside scheme we proposed. Authors: Cristina Banks-Leite, Renata Pardini, Leandro R. Tambosi, William D. Pearse, Adriana A. Bueno, Roberta T. Bruscagin, Thais H. Condez, Marianna Dixo, Alexandre T. Igari, Alexandre C. Martensen, Jean Paul Metzger

The profound influence of marine plankton on the global carbon cycle has been recognized for decades, particularly for photosynthetic microbes that form the base of ocean food chains. However, a comprehensive model of the carbon cycle is challenged by unicellular eukaryotes (protists) having evolved complex behavioral strategies and organismal interactions that extend far beyond photosynthetic lifestyles. As is also true for multicellular eukaryotes, these strategies and their associated physiological changes are difficult to deduce from genome sequences or gene repertoires—a problem compounded by numerous unknown function proteins. Here, we explore protistan trophic modes in marine food webs and broader biogeochemical influences. We also evaluate approaches that could resolve their activities, link them to biotic and abiotic factors, and integrate them into an ecosystems biology framework. Authors: Alexandra Z. Worden, Michael J. Follows, Stephen J. Giovannoni, Susanne Wilken, Amy E. Zimmerman, Patrick J. Keeling

The planetary boundaries framework defines a safe operating space for humanity based on the intrinsic biophysical processes that regulate the stability of the Earth system. Here, we revise and update the planetary boundary framework, with a focus on the underpinning biophysical science, based on targeted input from expert research communities and on more general scientific advances over the past 5 years. Several of the boundaries now have a two-tier approach, reflecting the importance of cross-scale interactions and the regional-level heterogeneity of the processes that underpin the boundaries. Two core boundaries—climate change and biosphere integrity—have been identified, each of which has the potential on its own to drive the Earth system into a new state should they be substantially and persistently transgressed. Authors: Will Steffen, Katherine Richardson, Johan Rockström, Sarah E. Cornell, Ingo Fetzer, Elena M. Bennett, Reinette Biggs, Stephen R. Carpenter, Wim de Vries, Cynthia A. de Wit, Carl Folke, Dieter Gerten, Jens Heinke, Georgina M. Mace, Linn M. Persson, Veerabhadran Ramanathan, Belinda Reyers, Sverker Sörlin

Knowledge of chemical reaction mechanisms can facilitate catalyst optimization, but extracting that knowledge from a complex system is often challenging. Here, we present a data-intensive method for deriving and then predictively applying a mechanistic model of an enantioselective organic reaction. As a validating case study, we selected an intramolecular dehydrogenative C-N coupling reaction, catalyzed by chiral phosphoric acid derivatives, in which catalyst-substrate association involves weak, noncovalent interactions. Little was previously understood regarding the structural origin of enantioselectivity in this system. Catalyst and substrate substituent effects were probed by means of systematic physical organic trend analysis. Plausible interactions between the substrate and catalyst that govern enantioselectivity were identified and supported experimentally, indicating that such an approach can afford an efficient means of leveraging mechanistic insight so as to optimize catalyst design. Authors: Anat Milo, Andrew J. Neel, F. Dean Toste, Matthew S. Sigman

Electric double layers (EDLs) of ionic liquids have been used in superconducting field-effect transistors as nanogap capacitors. Because of the freezing of the ionic motion below ~200 kelvin, modulations of the carrier density have been limited to the high-temperature regime. Here we observe carrier-doping–induced superconductivity in an organic Mott insulator with a photoinduced EDL based on a photochromic spiropyran monolayer. Because the spiropyran can isomerize reversibly between nonionic and zwitterionic isomers through photochemical processes, two distinct built-in electric fields can modulate the carrier density even at cryogenic conditions. Authors: Masayuki Suda, Reizo Kato, Hiroshi M. Yamamoto

Dental enamel, a hierarchical material composed primarily of hydroxylapatite nanowires, is susceptible to degradation by plaque biofilm–derived acids. The solubility of enamel strongly depends on the presence of Mg2+, F−, and CO32–. However, determining the distribution of these minor ions is challenging. We show—using atom probe tomography, x-ray absorption spectroscopy, and correlative techniques—that in unpigmented rodent enamel, Mg2+ is predominantly present at grain boundaries as an intergranular phase of Mg-substituted amorphous calcium phosphate (Mg-ACP). In the pigmented enamel, a mixture of ferrihydrite and amorphous iron-calcium phosphate replaces the more soluble Mg-ACP, rendering it both harder and more resistant to acid attack. These results demonstrate the presence of enduring amorphous phases with a dramatic influence on the physical and chemical properties of the mature mineralized tissue. Authors: Lyle M. Gordon, Michael J. Cohen, Keith W. MacRenaris, Jill D. Pasteris, Takele Seda, Derk Joester

Carbonyl oxides, or Criegee intermediates, are important transient species formed in the reactions of unsaturated hydrocarbons with ozone. Although direct detection of Criegee intermediates has recently been realized, the main atmospheric sink of Criegee intermediates remains unclear. We report ultraviolet absorption spectroscopic measurements of the lifetime of the simplest Criegee intermediate, CH2OO, at various relative humidity levels up to 85% at 298 kelvin. An extremely fast decay rate of CH2OO was observed at high humidity. The observed quadratic dependence of the decay rate on water concentration implied a predominant reaction with water dimer. On the basis of the water dimer equilibrium constant, the effective rate coefficient of the CH2OO + (H2O)2 reaction was determined to be 6.5 (±0.8) × 10−12 cubic centimeters per second. This work would help modelers to better constrain the atmospheric concentrations of CH2OO. Authors: Wen Chao, Jun-Ting Hsieh, Chun-Hung Chang, Jim Jr-Min Lin

The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca2+) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise “activity snapshot” of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca2+ and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies. Authors: Benjamin F. Fosque, Yi Sun, Hod Dana, Chao-Tsung Yang, Tomoko Ohyama, Michael R. Tadross, Ronak Patel, Marta Zlatic, Douglas S. Kim, Misha B. Ahrens, Vivek Jayaraman, Loren L. Looger, Eric R. Schreiter

A new Late Jurassic docodontan shows specializations for a subterranean lifestyle. It is similar to extant subterranean golden moles in having reduced digit segments as compared to the ancestral phalangeal pattern of mammaliaforms and extant mammals. The reduction of digit segments can occur in mammals by fusion of the proximal and intermediate phalangeal precursors, a developmental process for which a gene and signaling network have been characterized in mouse and human. Docodontans show a positional shift of thoracolumbar ribs, a developmental variation that is controlled by Hox9 and Myf5 genes in extant mammals. We argue that these morphogenetic mechanisms of modern mammals were operating before the rise of modern mammals, driving the morphological disparity in the earliest mammaliaform diversification. Authors: Zhe-Xi Luo, Qing-Jin Meng, Qiang Ji, Di Liu, Yu-Guang Zhang, April I. Neander

A new docodontan mammaliaform from the Middle Jurassic of China has skeletal features for climbing and dental characters indicative of an omnivorous diet that included plant sap. This fossil expands the range of known locomotor adaptations in docodontans to include climbing, in addition to digging and swimming. It further shows that some docodontans had a diet with a substantial herbivorous component, distinctive from the faunivorous diets previously reported in other members of this clade. This reveals a greater ecological diversity in an early mammaliaform clade at a more fundamental taxonomic level not only between major clades as previously thought. Authors: Qing-Jin Meng, Qiang Ji, Yu-Guang Zhang, Di Liu, David M. Grossnickle, Zhe-Xi Luo

Plastic debris in the marine environment is widely documented, but the quantity of plastic entering the ocean from waste generated on land is unknown. By linking worldwide data on solid waste, population density, and economic status, we estimated the mass of land-based plastic waste entering the ocean. We calculate that 275 million metric tons (MT) of plastic waste was generated in 192 coastal countries in 2010, with 4.8 to 12.7 million MT entering the ocean. Population size and the quality of waste management systems largely determine which countries contribute the greatest mass of uncaptured waste available to become plastic marine debris. Without waste management infrastructure improvements, the cumulative quantity of plastic waste available to enter the ocean from land is predicted to increase by an order of magnitude by 2025. Authors: Jenna R. Jambeck, Roland Geyer, Chris Wilcox, Theodore R. Siegler, Miriam Perryman, Anthony Andrady, Ramani Narayan, Kara Lavender Law

Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A β loop and a C-terminal membrane–anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3′ terminus, and vacate the active-site cavity during elongation. We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site. Authors: Todd C. Appleby, Jason K. Perry, Eisuke Murakami, Ona Barauskas, Joy Feng, Aesop Cho, David Fox, Diana R. Wetmore, Mary E. McGrath, Adrian S. Ray, Michael J. Sofia, S. Swaminathan, Thomas E. Edwards

The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 Å resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE–mediated disassembly of TJs. Authors: Yasunori Saitoh, Hiroshi Suzuki, Kazutoshi Tani, Kouki Nishikawa, Katsumasa Irie, Yuki Ogura, Atsushi Tamura, Sachiko Tsukita, Yoshinori Fujiyoshi

Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. Authors: Anuradha Illendula, John A. Pulikkan, Hongliang Zong, Jolanta Grembecka, Liting Xue, Siddhartha Sen, Yunpeng Zhou, Adam Boulton, Aravinda Kuntimaddi, Yan Gao, Roger A. Rajewski, Monica L. Guzman, Lucio H. Castilla, John H. Bushweller

When exposed to antigens, naïve B cells differentiate into different types of effector cells: antibody-producing plasma cells, germinal center cells, or memory cells. Whether an individual naïve B cell can produce all of these different cell fates remains unclear. Using a limiting dilution approach, we found that many individual naïve B cells produced only one type of effector cell subset, whereas others produced all subsets. The capacity to differentiate into multiple subsets was a characteristic of clonal populations that divided many times and resisted apoptosis, but was independent of isotype switching. Antigen receptor affinity also influenced effector cell differentiation. These findings suggest that diverse effector cell types arise in the primary immune response as a result of heterogeneity in responses by individual naïve B cells. Authors: Justin J. Taylor, Kathryn A. Pape, Holly R. Steach, Marc K. Jenkins

Lipids have traditionally been among the hardest biomolecules to study, but new technologies and techniques are gradually revealing more of the lipidome.Read the Feature (Full-Text HTML)Read the Feature (PDF)Read New Products (PDF) Author: Alan Dove

A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.

On this week's show: Updating the planetary boundaries framework, an accounting of ocean plastics, and a roundup of daily news stories.

s I retire from the office of chief executive of the American Association for the Advancement of Science (AAAS) and pass the baton to my very capable successor, physicist and former U.S. congressman Rush Holt, I have been reflecting on changes over the past decades both within the scientific enterprise and in its relationship with the rest of society. Many trends are cause for celebration, but others require remedial attention. On the positive side, new technologies have enabled new and very important scientific questions to be confronted, and a rise in collaborative, multidisciplinary science has fueled a remarkable pace of discovery. Science is also becoming more global in character as more countries invest in science and technology and fortify their infrastructures and science capacities. Science has never been more productive. And yet, the overall climate for science is more difficult than I have ever seen in my scientific career. This stunning state of contradiction indicates that there has never been a greater need, or a greater opportunity, for an international organization such as AAAS, whose mission is to advance science and serve society. Author: Alan I. Leshner

In science news around the world, molecular diagnostics company Myriad Genetics ends a long battle to defend its controversial patents on genetic tests for cancer risk, police search the Max Planck Institute for Biological Cybernetics in response to accusations of animal mistreatment by activists, researchers funded by the pharmaceutical company Roche—which makes Tamiflu—found that the drug helps combat influenza, a fire at the Russian Academy of Sciences destroys a significant portion of its documents, and the U.K. House of Commons votes overwhelmingly to allow researchers to pursue a fertility treatment called mitochondrial DNA replacement therapy. Also, the European Commission's former (and first) chief science adviser, microbiologist Anne Glover, tells reporters she doesn't regret saying that opposing genetically modified crops is a form of madness. And the first Science Ball opens its doors to debutantes and doctorates in Vienna, home of the waltz and of balls.

In addition to carving up the continents, the ice ages also tattoo the sea floor with rhythmic patterns, according to two studies published this week. At seafloor spreading centers, plates of ocean crust diverge and magma erupts in the gap, building new crust onto the plates' trailing edges. Parallel to these spreading centers are "abyssal hills": long, 100-meter-high ridges on the diverging plates, separated by valleys. It turns out that these periodic grooves reflect the timing of the ice ages. Ice ages are driven mainly by periodic variations in Earth's orbit and spin that alter sunlight in the Northern Hemisphere. During these periods, ice sheets trap so much frozen water that sea levels can drop a hundred meters or more. This reduces the pressure on the ocean floor and, in turn, speeds up the eruptions at the spreading centers—thickening the ocean plates and creating the abyssal hills, researchers say. The periodic strength of the eruptions helps explain the long-debated origin of the abyssal hills. Also intriguing is the question of whether emissions from seafloor volcanoes could be a feedback that helps bring about the end of ice ages. Author: Eric Hand

Since last April, a bipartisan team in the U.S. House of Representatives has led a high-profile initiative to speed the development of new medical treatments. Last week, the initiative bore its first fruit: a sweeping draft proposal released by Energy and Commerce Committee Chair Fred Upton (R–MI) that would overhaul many policies at the National Institutes of Health and the Food and Drug Administration. But Upton's draft had a bumpy rollout. His partner in the initiative, Diana DeGette (D–CO), announced that she did not endorse it. And although the document is attracting praise from many industry and research advocacy groups, some are concerned that it neglects basic research funding while extending overly generous terms to drug companies. Author: Kelly Servick

When the biggest discovery in cosmology in years officially unraveled last Friday, nobody was surprised. Nevertheless, cosmologists remain optimistic that such a discovery may come soon. Last March, cosmologists using a specialized telescope at the South Pole called BICEP2 reported that they had detected faint pinwheel-like swirls in the afterglow of the big bang—the cosmic microwave background—that would be direct evidence of cosmic inflation, a bizarre exponential growth spurt thought to have blown up the infant universe. But in September, data from Europe's Planck spacecraft suggested the signal was an artifact of dust in our galaxy. Now, a joint analysis by the BICEP and Planck teams confirms the dust explanation. Still, a gaggle of experiments in the works will have sensitivity to see a signal half as strong as the now-discredited one. And researchers are planning for a $100 million network of telescopes, to be deployed next decade, that would be 10 times more sensitive still. Evidence for inflation may come within a few years. Author: Adrian Cho