[Report] Reduced El Niño–Southern Oscillation during the Last Glacial Maximum

El Niño–Southern Oscillation (ENSO) is a major source of global interannual variability, but its response to climate change is uncertain. Paleoclimate records from the Last Glacial Maximum (LGM) provide insight into ENSO behavior when global boundary conditions (ice sheet extent, atmospheric partial pressure of CO2) were different from those today. In this work, we reconstruct LGM temperature variability at equatorial Pacific sites using measurements of individual planktonic foraminifera shells. A deep equatorial thermocline altered the dynamics in the eastern equatorial cold tongue, resulting in reduced ENSO variability during the LGM compared to the Late Holocene. These results suggest that ENSO was not tied directly to the east-west temperature gradient, as previously suggested. Rather, the thermocline of the eastern equatorial Pacific played a decisive role in the ENSO response to LGM climate. Authors: Heather L. Ford, A. Christina Ravelo, Pratigya J. Polissar

[Report] Linked canopy, climate, and faunal change in the Cenozoic of Patagonia

Vegetation structure is a key determinant of ecosystems and ecosystem function, but paleoecological techniques to quantify it are lacking. We present a method for reconstructing leaf area index (LAI) based on light-dependent morphology of leaf epidermal cells and phytoliths derived from them. Using this proxy, we reconstruct LAI for the Cenozoic (49 million to 11 million years ago) of middle-latitude Patagonia. Our record shows that dense forests opened up by the late Eocene; open forests and shrubland habitats then fluctuated, with a brief middle-Miocene regreening period. Furthermore, endemic herbivorous mammals show accelerated tooth crown height evolution during open, yet relatively grass-free, shrubland habitat intervals. Our Patagonian LAI record provides a high-resolution, sensitive tool with which to dissect terrestrial ecosystem response to changing Southern Ocean conditions during the Cenozoic. Authors: Regan E. Dunn, Caroline A. E. Strömberg, Richard H. Madden, Matthew J. Kohn, Alfredo A. Carlini

[Report] Expectations of brilliance underlie gender distributions across academic disciplines

The gender imbalance in STEM subjects dominates current debates about women’s underrepresentation in academia. However, women are well represented at the Ph.D. level in some sciences and poorly represented in some humanities (e.g., in 2011, 54% of U.S. Ph.D.’s in molecular biology were women versus only 31% in philosophy). We hypothesize that, across the academic spectrum, women are underrepresented in fields whose practitioners believe that raw, innate talent is the main requirement for success, because women are stereotyped as not possessing such talent. This hypothesis extends to African Americans’ underrepresentation as well, as this group is subject to similar stereotypes. Results from a nationwide survey of academics support our hypothesis (termed the field-specific ability beliefs hypothesis) over three competing hypotheses. Authors: Sarah-Jane Leslie, Andrei Cimpian, Meredith Meyer, Edward Freeland

[Report] Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection

The capacity of human norovirus (NoV), which causes >90% of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-λ, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system. Authors: Megan T. Baldridge, Timothy J. Nice, Broc T. McCune, Christine C. Yokoyama, Amal Kambal, Michael Wheadon, Michael S. Diamond, Yulia Ivanova, Maxim Artyomov, Herbert W. Virgin

[Report] Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity

Norovirus gastroenteritis is a major public health burden worldwide. Although fecal shedding is important for transmission of enteric viruses, little is known about the immune factors that restrict persistent enteric infection. We report here that although the cytokines interferon-α (IFN-α) and IFN-β prevented the systemic spread of murine norovirus (MNoV), only IFN-λ controlled persistent enteric infection. Infection-dependent induction of IFN-λ was governed by the MNoV capsid protein and correlated with diminished enteric persistence. Treatment of established infection with IFN-λ cured mice in a manner requiring nonhematopoietic cell expression of the IFN-λ receptor, Ifnlr1, and independent of adaptive immunity. These results suggest the therapeutic potential of IFN-λ for curing virus infections in the gastrointestinal tract. Authors: Timothy J. Nice, Megan T. Baldridge, Broc T. McCune, Jason M. Norman, Helen M. Lazear, Maxim Artyomov, Michael S. Diamond, Herbert W. Virgin

[Report] Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors

Cancer cells rely on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative mortality. ALT is mediated by recombination and is prevalent in a subset of human cancers, yet whether it can be exploited therapeutically remains unknown. Loss of the chromatin-remodeling protein ATRX associates with ALT in cancers. Here, we show that ATRX loss compromises cell-cycle regulation of the telomeric noncoding RNA TERRA and leads to persistent association of replication protein A (RPA) with telomeres after DNA replication, creating a recombinogenic nucleoprotein structure. Inhibition of the protein kinase ATR, a critical regulator of recombination recruited by RPA, disrupts ALT and triggers chromosome fragmentation and apoptosis in ALT cells. The cell death induced by ATR inhibitors is highly selective for cancer cells that rely on ALT, suggesting that such inhibitors may be useful for treatment of ALT-positive cancers. Authors: Rachel Litman Flynn, Kelli E. Cox, Maya Jeitany, Hiroaki Wakimoto, Alysia R. Bryll, Neil J. Ganem, Francesca Bersani, Jose R. Pineda, Mario L. Suvà, Cyril H. Benes, Daniel A. Haber, Francois D. Boussin, Lee Zou

[Report] Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection

CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. Authors: Pablo Penaloza-MacMaster, Daniel L. Barber, E. John Wherry, Nicholas M. Provine, Jeffrey E. Teigler, Lily Parenteau, Stephen Blackmore, Erica N. Borducchi, Rafael A. Larocca, Kathleen B. Yates, Hao Shen, W. Nicholas Haining, Rami Sommerstein, Daniel D. Pinschewer, Rafi Ahmed, Dan H. Barouch

[Report] Charge ordering in the electron-doped superconductor Nd2–xCexCuO4

In cuprate high-temperature superconductors, an antiferromagnetic Mott insulating state can be destabilized toward unconventional superconductivity by either hole or electron doping. In hole-doped (p-type) cuprates, a charge ordering (CO) instability competes with superconductivity inside the pseudogap state. We report resonant x-ray scattering measurements that demonstrate the presence of charge ordering in the n-type cuprate Nd2–xCexCuO4 near optimal doping. We find that the CO in Nd2–xCexCuO4 occurs with similar periodicity, and along the same direction, as in p-type cuprates. However, in contrast to the latter, the CO onset in Nd2–xCexCuO4 is higher than the pseudogap temperature, and is in the temperature range where antiferromagnetic fluctuations are first detected. Our discovery opens a parallel path to the study of CO and its relationship to antiferromagnetism and superconductivity. Authors: Eduardo H. da Silva Neto, Riccardo Comin, Feizhou He, Ronny Sutarto, Yeping Jiang, Richard L. Greene, George A. Sawatzky, Andrea Damascelli

[Report] Semiconductor double quantum dot micromaser

The coherent generation of light, from masers to lasers, relies upon the specific structure of the individual emitters that lead to gain. Devices operating as lasers in the few-emitter limit provide opportunities for understanding quantum coherent phenomena, from terahertz sources to quantum communication. Here we demonstrate a maser that is driven by single-electron tunneling events. Semiconductor double quantum dots (DQDs) serve as a gain medium and are placed inside a high-quality factor microwave cavity. We verify maser action by comparing the statistics of the emitted microwave field above and below the maser threshold. Authors: Y.-Y. Liu, J. Stehlik, C. Eichler, M. J. Gullans, J. M. Taylor, J. R. Petta

[Report] An Aharonov-Bohm interferometer for determining Bloch band topology

The geometric structure of a single-particle energy band in a solid is fundamental for a wide range of many-body phenomena and is uniquely characterized by the distribution of Berry curvature over the Brillouin zone. We realize an atomic interferometer to measure Berry flux in momentum space, in analogy to an Aharonov-Bohm interferometer that measures magnetic flux in real space. We demonstrate the interferometer for a graphene-type hexagonal optical lattice loaded with bosonic atoms. By detecting the singular π Berry flux localized at each Dirac point, we establish the high momentum resolution of this interferometric technique. Our work forms the basis for a general framework to fully characterize topological band structures. Authors: L. Duca, T. Li, M. Reitter, I. Bloch, M. Schleier-Smith, U. Schneider

[Report] Universal solvent restructuring induced by colloidal nanoparticles

Colloidal nanoparticles, used for applications from catalysis and energy applications to cosmetics, are typically embedded in matrixes or dispersed in solutions. The entire particle surface, which is where reactions are expected to occur, is thus exposed. Here, we show with x-ray pair distribution function analysis that polar and nonpolar solvents universally restructure around nanoparticles. Layers of enhanced order exist with a thickness influenced by the molecule size and up to 2 nanometers beyond the nanoparticle surface. These results show that the enhanced reactivity of solvated nanoparticles includes a contribution from a solvation shell of the size of the particle itself. Authors: Mirijam Zobel, Reinhard B. Neder, Simon A. J. Kimber

[Report] Observation of Fermi arc surface states in a topological metal

The topology of the electronic structure of a crystal is manifested in its surface states. Recently, a distinct topological state has been proposed in metals or semimetals whose spin-orbit band structure features three-dimensional Dirac quasiparticles. We used angle-resolved photoemission spectroscopy to experimentally observe a pair of spin-polarized Fermi arc surface states on the surface of the Dirac semimetal Na3Bi at its native chemical potential. Our systematic results collectively identify a topological phase in a gapless material. The observed Fermi arc surface states open research frontiers in fundamental physics and possibly in spintronics. Authors: Su-Yang Xu, Chang Liu, Satya K. Kushwaha, Raman Sankar, Jason W. Krizan, Ilya Belopolski, Madhab Neupane, Guang Bian, Nasser Alidoust, Tay-Rong Chang, Horng-Tay Jeng, Cheng-Yi Huang, Wei-Feng Tsai, Hsin Lin, Pavel P. Shibayev, Fang-Cheng Chou, Robert J. Cava, M. Zahid Hasan

[New Products] New Products

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

[Business Office Feature] The Art and Science of Traditional Medicine Part 2: Multidisciplinary Approaches for Studying Traditional Medicine

In this second of three special supplements, herbal genomics as a novel approach for revolutionizing research on, and ultimately use of, traditional herbal medicines and other materia medica, as well as advances in their quality control and standardization, is highlighted. A prominent focus is the U.S. Food and Drug Administration’s practical framework for developing botanicals (including traditional medicines) into new drugs based on the same standards as small molecule drugs. The application of mechanistic studies to drug discovery and development from traditional therapies is discussed, with an emphasis on preclinical toxicology assessments, pharmacovigilance, comparative effectiveness research, and the practice of "P4" medicine, particularly in the context of influenza, ischemic heart disease, stroke, and cancer. Read the special supplement (PDF, 6.5MB)This special supplement brought to you by the Science/AAAS Custom Publishing Office.

[Editorial] Toward designing safer chemicals

One year ago, an industrial coal-processing liquid contaminated the Elk River in West Virginia and affected the tap water of 15% of the state's population. The spill was declared a federal disaster, and ongoing investigations remain. Last month, a report assessing the water and health impacts of the Elk River spill pointed to the lack of a sound scientific approach for responding to and recovering from such incidents.* This year also marks 5 years since the Deepwater Horizon oil spill in the Gulf of Mexico, and last month brought the 30-year anniversary of the Bhopal gas tragedy that killed thousands, considered the world's worst industrial disaster. Despite our best efforts and intentions, human-made chemicals continue to be released into the environment, often with unquantified and potentially unquantifiable deleterious consequences. The questions posed to science are how to better understand the nature of synthetic substances in order to predict their potential adverse impacts on humans and the biosphere, and how do we design future substances to eliminate the need for engineered control systems. Authors: Julie B. Zimmerman, Paul T. Anastas

[In Brief] This week's section

In science news around the world, the U.S. Fish and Wildlife Service expands the range of the rare Mexican gray wolf, genetic analysis company 23andMe announces new deals to share its data with drug developers, two leading cancer groups call for e-cigarette regulation, the Federation of American Societies for Experimental Biology suggests ways for the National Institutes of Health to stretch its flat budget, and a Chinese developer's scheme to use HIV-infected people to harass residents resisting housing demolition reveals lingering anti-HIV prejudice. Also, Brazil's new science minister is a reputed climate skeptic, causing some scientists to worry about the country's environmental future. And Science talks with Microsoft Research Managing Director Eric Horvitz about his One Hundred Year Study on Artificial Intelligence, launched late last year.

[In Depth] High hopes for Guinean vaccine trial

The push to test Ebola vaccines in the field is accelerating. Two candidates may go into phase III trials in a matter of weeks; a third one has just entered a phase I trial. Researchers have designed very different phase III studies for Liberia, Sierra Leone, and Guinea, the three countries with ongoing virus transmission. One problem they're facing is that the number of new cases has dropped sharply in Liberia and is beginning to ebb in Sierra Leone. That's why many scientists say Guinea—where researchers plan to try a highly unusual ring vaccination design—is the most promising testing ground. Author: Martin Enserink

[In Depth] All in the (bigger) family

A decade of genetic data and other evidence has persuaded most researchers that insects and crustaceans, long considered widely separated branches of the arthropod family, actually belong together. The new arthropod tree puts hexapods—six-limbed creatures that include insects, springtails, and silverfish—as closer kin to crabs, lobster, shrimp, and crayfish than those "standard" crustaceans are to others such as seed shrimp. Traditionally, insect and crustacean scientists have taken different approaches, even when they have studied similar problems. Now they are exploring the consequences of the new family tree, and last week at a special symposium of the annual meeting of the Society for Integrative and Comparative Biology, researchers reported new parallels between these two very successful groups of animals and new insights about what it took for an ancient crustacean to give rise to insects. Author: Elizabeth Pennisi

[In Depth] Google[x] searches for ways to boost cancer immunotherapy

Google[x], a semisecretive branch of the company most famous for its search engine, hosted an invitation-only summit on cancer immunotherapy to see how it might help speed discovery in the burgeoning field. Andy Conrad, head of the Google[x] life sciences program—which now has a team of 100—urged the participants to think big, along the lines of "10x, not 10%." For 2 days, the Google[x] team members mixed it up with leading immunologists, oncologists, materials scientists, imaging specialists, and engineers, and in the end they came up with two top-priority projects that the company plans to help fund and coordinate. Author: Jon Cohen

[In Depth] Throwing a lifeline to a one-time Arab science power

The U.S. government is stepping up efforts to restore the intellectual capital that Iraq will need to rebuild. The State Department's 7-year-old Iraq Science Fellowship Program has trained 52 Iraqi scientists in various specialties. This month it will be joined by a second fellowship program, funded by the U.S. Defense Threat Reduction Agency, to bring several scientists a year to the United States to train in top labs. The new program will focus chiefly on biologists in dual-use areas—those whose research could be used to create new toxins or biological weapons—and it will emphasize biosecurity and threat reduction. Author: Richard Stone

[In Depth] Backlash greets ‘bad luck’ cancer study and coverage

Two weeks ago, Science published a paper by Bert Vogelstein and Cristian Tomasetti of Johns Hopkins University, which put forth a mathematical analysis of the genesis of cancer and sought to explain variations in risk at different tissues. The paper, and especially the news coverage (including by Science) that followed, came under heavy criticism and generated hundreds of comments. Journalists were accused of misinterpreting the study's results. Although some praised the paper for elucidating the role that chance—the accumulation of random mutations in stem cells—plays in cancer, others argued that the authors' conclusions were flawed or oversimplified. Science examines how this story was communicated and the challenges inherent to streamlining complex biology and statistics for experts and nonexperts alike. Author: Jennifer Couzin-Frankel

[In Depth] Devices team up to boost solar power

The most efficient photovoltaics are devices called tandems that consist of stacks of solar cells, each tailored to absorb a different slice of the solar spectrum. This complexity makes them expensive and thus better suited for use in space where the extra power they produce is worth the added cost. But now, solar cell researchers are looking to create low-cost, high-efficiency tandems using perovskites, the hottest and cheapest new solar cell material out there. It's still early days, and progress on perovskite tandems remains modest. But researchers say the path to highly efficient perovskite tandems is clear and is expected to occur within the next year or two. Author: Robert F. Service

[Feature] The cancer stem cell gamble

Renowned Massachusetts Institute of Technology cancer biologist Robert Weinberg is staking part of his considerable reputation on a bold theory that has divided the cancer field. Weinberg and others contend that tumors contain a small number of cells that are distinctive because they resemble the stem cells that give rise to normal tissues. These cancer seeds, able to resist chemotherapy and spring back months or years after treatment, may explain the tragic relapses people often experience. Give patients a drug that targets these cancer stem cells, the thinking goes, and the disease can be kept under control. Verastem Inc., a company Weinberg co-founded, is one of several that are launching a new round of clinical trials to find out whether the theory actually works. Beyond the promise of changing cancer care, the financial stakes are huge. But as many in the field acknowledge, it may be difficult to draw definitive conclusions from these trials. Author: Jocelyn Kaiser

[Perspective] The birth of the geological map

In 1815, William Smith, an English canal surveyor and land drainer, provided the young science of geology with the first true geological map of an entire country (see the first figure). Two hundred years on, Smith's map has become an icon of Earth science, and the basic principles he developed and applied are still used in interpreting rock sequences and making geological maps. Author: Tom Sharpe

[Perspective] New SQUID on the Bloch

Schrödinger's famous cat showed us that the matter waves inside an atom could manifest on macroscopic scales, but the real workhorse of the quantum world is the SQUID, or superconducting quantum interference device. This piece of technology is the key component of some hospital MRI (magnetic resonance imaging) scanners and other medical equipment because of its ability to detect tiny magnetic fields. On page 288 of this issue, Duca et al. (1) show that identical experimental principles can be used to detect the phases of the waves describing the motion of atoms in a periodic potential, known as Bloch states. Electrons moving in a crystal lattice are described by the same states, but although they are central to solid-state physics, their properties are usually inferred from other measurements—conductivity, for example. The study by Duca et al. provides a proof-of-principle demonstration of a new type of interferometry capable of providing much more detailed information than existing techniques. Author: Austen Lamacraft

[Perspective] Interfering with interferons

Living organisms must resist viral infection. In mammals, both infected cells and innate immune cells release signals (cytokines) that program the infected cells for antiviral defense, as well as alert neighboring cells that trouble is afoot. These signals—exemplified by the type I (α and β), type II (γ), and type III (λ) interferons (IFNs)—control the mammalian response against the vast majority of viruses. The host's control of an enteric pathogen, rotavirus, requires type III IFNs (1, 2). On page 269 and 266 of this issue, Nice (3) and Baldridge (4), respectively, show that protection provided by λ IFNs is generalizable to another enteric pathogen, norovirus. Notably, this protection is independent from the adaptive immune response, which has long thought to be absolutely required for clearing viral infection. Authors: Jessica Wilks, Tatyana Golovkina

[Perspective] Gender inequality in science

Why are women underrepresented in many areas of science, technology, engineering, and mathematics (STEM)? This is a question with no easy answers. In science, as in many areas of life, bias against women exists (1), but researchers disagree on how much bias matters: Some suggest that the effects of bias accumulate over time to shape careers (2), whereas others argue that gender differences in preferences are much more important (3). However, it is likely impossible to disentangle the effects of societal bias and individual preferences, because people's understanding of gender differences shape their preferences (4). Research suggests differences in innate ability are unlikely to play a major role (3), but one route to more equal representation across academic fields might be convincing both women and men that this is true. On page 262 of this issue, Leslie et al. (5) show that how ability is viewed within a field plays a key role in how well women are represented. Author: Andrew M. Penner

[Policy Forum] Disclosing patents' secrets

The patent system is built on a grand bargain: To gain exclusive rights to practice their inventions, inventors must disclose their proprietary knowledge publicly. Economists have studied incentive benefits of exclusivity while implicitly assuming that disclosure of know-how in patent applications is costly for inventors. Yet, apart from facilitating diffusion of knowledge, disclosing know-how in a patent may privately benefit inventors by deterring rivals' duplicative research and development (R&D), preempting competitors' efforts to patent similar technology, and reducing informational asymmetries between patentees and potential investors [supplementary materials (SM)]. Understanding to what extent disclosure is viewed as a cost or a benefit by patenting inventors provides insights into our complex patent system and allows better policy-making to advance the diffusion of technical knowledge. Authors: Stuart Graham, Deepak Hegde

[Book Review] Fueling the future

There is no such thing as a "free lunch" in the energy sector, which means we face tough choices when it comes to power. But how do we weigh our options? Matthew E. Kahn considers how we make decisions about energy in the 21st century in a review of Cheap and Clean: How Americans Think About Energy in the Age of Global Warming.