[In Depth] Africa's soil engineers: Termites

Although we all tend to think about large mammals as being the big dominant drivers of what's happening in the savanna, termites and their mounds are proving ever more influential. Indigenous people have long used soil from termite mounds for farming. Studies have long shown termites, by retrieving vegetation, help concentrate nitrogen, phosphorous, and organic material in the mounds. These nutrient islands are the savanna's supermarkets, supporting both plant-eating and predatory insects, as well as spiders, lizards, and large grazers, such as elephants. They occur in polka-dot arrays, spaced to maximize the number of mounds while minimizing territorial conflicts. By modeling the interactions of termites, rainfall, soil, and plants, researchers now show that the termite mounds are an insurance policy against climate change, protecting the vegetation on them from water scarcity. Author: Elizabeth Pennisi

[In Depth] Japanese neutrino physicists think really big

Japan has already made its mark in research into the wispy, elementary particles known as neutrinos. In the mid-1980s, the Kamiokande detector conducted groundbreaking observations of neutrinos emanating from the sun, the atmosphere, and a supernova. The work later won a Nobel Prize in physics. In the mid-1990s, observations at that detector's larger successor, Super-Kamiokande, demonstrated that neutrinos have mass, upsetting previous theories. Now Japanese physicists are thinking really big with a plan to build Hyper-Kamiokande, which would be the largest neutrino detector ever. Researchers believe this behemoth will allow them to determine the remaining unknown properties of neutrinos, study the early universe, and probe why matter is more common than antimatter. Scientists from 13 countries this past weekend formally launched a protocollaboration to develop a detailed design they can take to funding agencies in hopes of getting the $800 million or so needed to build the detector. They hope to start construction in 2018 and start taking data in 2025. Author: Dennis Normile

[In Depth] Budget for 2016 accentuates the practical

"Making it real" is the key message that U.S. scientists should take from the 2016 budget that President Barack Obama submitted to Congress this week. His proposed $4 trillion budget shatters the spending caps from a 10-year agreement reached in 2011 to reduce the federal deficit, using revenues from higher taxes on the wealthy. But the overall 7.2% increase allocated for all discretionary spending exceeds the percentage allocated to most agencies that support academic research, with the emphasis on applied research that addresses pressing societal problems. The White House had already announced initiatives on precision medicine and fighting antibiotic resistance, and the president's new budget also contains large increases in such areas as advanced manufacturing, energy technologies, and climate monitoring and mitigation. The budget debate now moves to Congress, which is likely to resist most of the spending increases. A yearlong battle is likely, with scientists as interested bystanders. Author: Jeffrey Mervis

[In Depth] Biomedical initiatives get top billing in budget rollout

Days before the release of the overall federal budget request, the White House began talking up two new flagship scientific efforts. The $215 million Precision Medicine Initiative, first mentioned in President Barack Obama's 20 January State of the Union address, aims to advance personalized medicine in part by assembling a database containing genetic and medical information from at least 1 million Americans. The other is a roughly $1.2 billion multiagency effort to combat the mounting public health crisis of antibiotic-resistant infections. The National Institutes of Health, which would receive an overall 3.3% increase to $31.3 billion, would play a key role in both campaigns. The two initiatives have drawn encouraging words from members of Congress in both parties. Authors: Jocelyn Kaiser, Kelly Servick

[Feature] A classroom experiment

The National Science Foundation (NSF) has poured half a billion dollars into the Robert Noyce Teacher Scholarship Program since it was launched in 2003. The program is meant to draw those with STEM (science, technology, engineering, and math) degrees into teaching at high-needs public schools, on the assumption that students would learn more science and math if they were taught by those who know and love the subjects. Several thousand Noyce-trained teachers have been placed in these schools. But so far the program hasn't moved the needle on student achievement, or even on the overall supply of well-prepared STEM teachers. The reasons are complicated. And many of the factors that will ultimately determine the success or failure of the program, including attitudes toward the teaching profession and the myriad factors that affect how students learn, lie outside NSF's power to control. Author: Jeffrey Mervis

[Policy Forum] Where is Silicon Valley?

Although economists, politicians, and business leaders have long emphasized the importance of entrepreneurship (1, 2), defining and characterizing entrepreneurship has been elusive (3, 4). Researchers have been unable to systematically connect the type of high-impact entrepreneurship found in regions such as Silicon Valley with the overall incidence of entrepreneurship in the population (5–7). This has important implications: Researchers arrive at alternative conclusions about roles and patterns of entrepreneurship (8–10), and policy-makers are given conflicting recommendations about whether or how to promote entrepreneurship for economic and social progress (11, 12). Authors: Jorge Guzman, Scott Stern

[Perspective] There goes the macrophage neighborhood

The lymph node is a highly structured organ optimized for generating adaptive immune responses. Lymph fluid carrying pathogens and their antigens from infected tissue is first distributed into a large cavity just beneath the node's surface, which is populated by a dense layer of specialized macrophages. These subcapsular sinus (SCS) macrophages filter incoming lymph, capture pathogens, and relay pathogen-derived antigen to B cells in subjacent follicles, provoking them to produce antibodies (see the figure). At the original infection site, migratory dendritic cells (DCs) are activated, acquire antigen, and deliver it to the node through the lymph, generating a secondary wave of immune cell activation. Until now, this influx of DCs has been viewed as beneficial to the host, as they activate T cells within the node's paracortex. However, on page 667 of this issue, Gaya et al. (1) demonstrate that incoming DCs can be harmful. These cells can disrupt the SCS macrophage layer and reduce the host's ability to mount a humoral (antibody) response to a secondary pathogen. Author: Heather D. Hickman

[Perspective] Taking temperature at the nanoscale

Measuring temperature has become commonplace since Fahrenheit, Celsius, and others introduced thermometers and temperature scales in the 18th century. However, the definition of temperature is not at all obvious, as it is now described as a statistical quantity given by the rate of change of entropy with respect to the internal energy of a system with volume and number of particles held constant. This is by itself not an easy concept to grasp. In addition, determining temperature raises thermodynamical questions when considering systems with further and further reduced dimensions (1). Consequently, measuring temperature at the nanoscale constitutes a challenge in many fields of science and technology. On page 629 of this issue, Mecklenburg et al. (2) report how they have elegantly met this challenge. Author: Christian Colliex

[Perspective] Our skewed sense of space

The hippocampus is the brain region where spatial maps of our surroundings are encoded. A specific location will activate a set of neurons called place cells to represent the particular place. What happens as the number of environments encountered increases? Does the hippocampus continually create and store distinct independent “maps” for each locale, or can place cells be recruited for more than one map to generalize across locales? It appears that both mechanisms contribute in unique ways. Author: György Buzsáki

[Perspective] A Me6Age for pluripotency

Cell-fate decisions are orchestrated by global changes in gene expression, some of which are driven by epigenetic alterations, often including methylation of DNA. Embryonic stem cells (ESCs) have been used to decipher many of the critical factors underlying cell-fate decisions. Mouse ESCs exist in several different pluripotent states, notably naïve or ground-state ESCs and primed epiblast stem cells (EpiSCs), which resemble pre- and post-implantation–stage embryos, respectively (1, 2). New research now reveals another role for nucleic acid methylation in stem cell–fate determination, but of RNA rather than DNA—at position six of the adenosine base (m6A). Two recent papers, by Geula et al. (3) in Science Express and Batista et al. (4), show that m6A is involved in regulating stem cell maintenance and cell-fate decisions through its modulation of RNA stability and translation. Authors: Hendrik G. Stunnenberg, Michiel Vermeulen, Yaser Atlasi

[Perspective] The coordination chemistry of nanocrystal surfaces

In the 1990s, when quantum confined colloidal semiconductor nanocrystals (NCs, or quantum dots) were first synthesized with narrow size distributions, there was an explosion of effort to harness their bright and narrow luminescence for optoelectronic devices and fluorescence labeling (1). However, the surfactant ligands that stabilized NCs also influenced their electronic structure and optical properties. Encapsulating the NC cores within an insulating inorganic shell reduced the effect of surface structure on charge recombination (2) and forced the radiative recombination of photoexcited charges. These structures greatly increased the photoluminescence quantum yield (PLQY) and enabled their recent use in liquid crystal displays. However, PLQYs of core-shell nanocrystals remain sensitive to their surfaces and if NCs are to be useful within electrical devices, such as photovoltaic (PV) cells, the complex relation between their surface structure and their frontier orbital structure must be better understood. Author: Jonathan Owen

[Perspective] How a virus travels the world

In November and December 2014, highly pathogenic avian influenza (HPAI) viruses of the H5 subtype originating from China were detected in poultry and wild birds in various countries of Asia and Europe, and, for the first time, in North America. These incursions of newly emerging HPAI H5 viruses constitute a threat to animal and potentially human health and raise questions about the routes of transmission. Authors: Josanne H. Verhagen, Sander Herfst, Ron A. M. Fouchier

[Book Review] Surrounded by science

The natural history museum is an example of a 19th-century invention that still has momentum in the 21st century. In a way, the continued presence of museums in our modern world is as surprising as if one were to see a fleet of horse-drawn carriages hurtling down the highway at 75 mph. Life on Display, by historians Karen A. Rader and Victoria E. M. Cain, focuses on the evolution of U.S. science and nature museums from the late 19th century to the early 21st century, stitching together a number of surprising insights into an excellent history. Author: Kirk R. Johnson

[Book Review] Breaking bad science

London newsstands can strike Americans as remarkable, both for the number of different papers being sold and for their alarming headlines. Most U.S. cities are lucky to have a single daily newspaper—shrinking in both physical size and circulation—with fairly staid contents. In contrast, Britain has about 10 daily newspapers that contend for a national audience. Their circulations are also slipping, but the fact that they are competing for readers makes their coverage colorful by American standards. Author: Joel Best

[Technical Comment] Comment on “A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity”

Sayou et al. (Reports, 7 February 2014, p. 645) proposed a new model for evolution of transcription factors without gene duplication, using LEAFY as an archetype. Their proposal contradicts the evolutionary history of plants and ignores evidence that LEAFY evolves through gene duplications. Within their data set, we identified a moss with multiple LEAFY orthologs, which contests their model and supports that LEAFY evolves through duplications. Authors: Jacob O. Brunkard, Anne M. Runkel, Patricia C. Zambryski

[Technical Response] Response to Comment on “A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity”

Brunkard et al. propose that the identification of novel LEAFY sequences contradicts our model of evolution through promiscuous intermediates. Based on the debate surrounding land plant phylogeny and on our analysis of these interesting novel sequences, we explain why there is no solid evidence to disprove our model. Authors: Samuel F. Brockington, Edwige Moyroud, Camille Sayou, Marie Monniaux, Max H. Nanao, Emmanuel Thévenon, Hicham Chahtane, Norman Warthmann, Michael Melkonian, Yong Zhang, Gane Ka-Shu Wong, Detlef Weigel, Renaud Dumas, François Parcy

[Review] Undergraduate research experiences: Impacts and opportunities

Most undergraduates give high ratings to research experiences. Studies report that these experiences improve participation and persistence, often by strengthening students’ views of themselves as scientists. Yet, the evidence for these claims is weak. More than half the 60 studies reviewed rely on self-report surveys or interviews. Rather than introducing new images of science, research experiences may reinforce flawed images especially of research practices and conceptual understanding. The most convincing studies show benefits for mentoring and for communicating the nature of science, but the ideas that students learn are often isolated or fragmented rather than integrated and coherent. Rigorous research is needed to identify ways to design research experiences so that they promote integrated understanding. These studies need powerful and generalizable assessments that can document student progress, help distinguish effective and ineffective aspects of the experiences, and illustrate how students interpret the research experiences they encounter. To create research experiences that meet the needs of interested students and make effective use of scarce resources, we encourage systematic, iterative studies with multiple indicators of success. Authors: Marcia C. Linn, Erin Palmer, Anne Baranger, Elizabeth Gerard, Elisa Stone

[Research Article] Combinatorial labeling of single cells for gene expression cytometry

We present a technically simple approach for gene expression cytometry combining next-generation sequencing with stochastic barcoding of single cells. A combinatorial library of beads bearing cell- and molecular-barcoding capture probes is used to uniquely label transcripts and reconstruct the digital gene expression profile of thousands of individual cells in a single experiment without the need for robotics or automation. We applied the technology to dissect the human hematopoietic system and to characterize heterogeneous response to in vitro stimulation. High sensitivity is demonstrated by detection of low-abundance transcripts and rare cells. Under current implementation, the technique can analyze a few thousand cells simultaneously and can readily scale to 10,000s or 100,000s of cells. Authors: H. Christina Fan, Glenn K. Fu, Stephen P. A. Fodor

[Report] Nanoscale temperature mapping in operating microelectronic devices

Modern microelectronic devices have nanoscale features that dissipate power nonuniformly, but fundamental physical limits frustrate efforts to detect the resulting temperature gradients. Contact thermometers disturb the temperature of a small system, while radiation thermometers struggle to beat the diffraction limit. Exploiting the same physics as Fahrenheit’s glass-bulb thermometer, we mapped the thermal expansion of Joule-heated, 80-nanometer-thick aluminum wires by precisely measuring changes in density. With a scanning transmission electron microscope and electron energy loss spectroscopy, we quantified the local density via the energy of aluminum’s bulk plasmon. Rescaling density to temperature yields maps with a statistical precision of 3 kelvin/hertz−1/2, an accuracy of 10%, and nanometer-scale resolution. Many common metals and semiconductors have sufficiently sharp plasmon resonances to serve as their own thermometers. Authors: Matthew Mecklenburg, William A. Hubbard, E. R. White, Rohan Dhall, Stephen B. Cronin, Shaul Aloni, B. C. Regan

[Report] Asynchronous rotation of Earth-mass planets in the habitable zone of lower-mass stars

Planets in the habitable zone of lower-mass stars are often assumed to be in a state of tidally synchronized rotation, which would considerably affect their putative habitability. Although thermal tides cause Venus to rotate retrogradely, simple scaling arguments tend to attribute this peculiarity to the massive Venusian atmosphere. Using a global climate model, we show that even a relatively thin atmosphere can drive terrestrial planets’ rotation away from synchronicity. We derive a more realistic atmospheric tide model that predicts four asynchronous equilibrium spin states, two being stable, when the amplitude of the thermal tide exceeds a threshold that is met for habitable Earth-like planets with a 1-bar atmosphere around stars more massive than ~0.5 to 0.7 solar mass. Thus, many recently discovered terrestrial planets could exhibit asynchronous spin-orbit rotation, even with a thin atmosphere. Authors: Jérémy Leconte, Hanbo Wu, Kristen Menou, Norman Murray

[Report] Origin of dramatic oxygen solute strengthening effect in titanium

Structural alloys are often strengthened through the addition of solute atoms. However, given that solute atoms interact weakly with the elastic fields of screw dislocations, it has long been accepted that solution hardening is only marginally effective in materials with mobile screw dislocations. By using transmission electron microscopy and nanomechanical characterization, we report that the intense hardening effect of dilute oxygen solutes in pure α-Ti is due to the interaction between oxygen and the core of screw dislocations that mainly glide on prismatic planes. First-principles calculations reveal that distortion of the interstitial sites at the screw dislocation core creates a very strong but short-range repulsion for oxygen that is consistent with experimental observations. These results establish a highly effective mechanism for strengthening by interstitial solutes. Authors: Qian Yu, Liang Qi, Tomohito Tsuru, Rachel Traylor, David Rugg, J. W. Morris, Mark Asta, D. C. Chrzan, Andrew M. Minor

[Report] Programming colloidal phase transitions with DNA strand displacement

DNA-grafted nanoparticles have been called “programmable atom-equivalents”: Like atoms, they form three-dimensional crystals, but unlike atoms, the particles themselves carry information (the sequences of the grafted strands) that can be used to “program” the equilibrium crystal structures. We show that the programmability of these colloids can be generalized to the full temperature-dependent phase diagram, not just the crystal structures themselves. We add information to the buffer in the form of soluble DNA strands designed to compete with the grafted strands through strand displacement. Using only two displacement reactions, we program phase behavior not found in atomic systems or other DNA-grafted colloids, including arbitrarily wide gas-solid coexistence, reentrant melting, and even reversible transitions between distinct crystal phases. Authors: W. Benjamin Rogers, Vinothan N. Manoharan

[Report] Direct observation and kinetics of a hydroperoxyalkyl radical (QOOH)

Oxidation of organic compounds in combustion and in Earth’s troposphere is mediated by reactive species formed by the addition of molecular oxygen (O2) to organic radicals. Among the most crucial and elusive of these intermediates are hydroperoxyalkyl radicals, often denoted “QOOH.” These species and their reactions with O2 are responsible for the radical chain branching that sustains autoignition and are implicated in tropospheric autoxidation that can form low-volatility, highly oxygenated organic aerosol precursors. We report direct observation and kinetics measurements of a QOOH intermediate in the oxidation of 1,3-cycloheptadiene, a molecule that offers insight into both resonance-stabilized and nonstabilized radical intermediates. The results establish that resonance stabilization dramatically changes QOOH reactivity and, hence, that oxidation of unsaturated organics can produce exceptionally long-lived QOOH intermediates. Authors: John D. Savee, Ewa Papajak, Brandon Rotavera, Haifeng Huang, Arkke J. Eskola, Oliver Welz, Leonid Sheps, Craig A. Taatjes, Judit Zádor, David L. Osborn

[Report] A rational strategy for the realization of chain-growth supramolecular polymerization

Over the past decade, major progress in supramolecular polymerization has had a substantial effect on the design of functional soft materials. However, despite recent advances, most studies are still based on a preconceived notion that supramolecular polymerization follows a step-growth mechanism, which precludes control over chain length, sequence, and stereochemical structure. Here we report the realization of chain-growth polymerization by designing metastable monomers with a shape-promoted intramolecular hydrogen-bonding network. The monomers are conformationally restricted from spontaneous polymerization at ambient temperatures but begin to polymerize with characteristics typical of a living mechanism upon mixing with tailored initiators. The chain growth occurs stereoselectively and therefore enables optical resolution of a racemic monomer. Authors: Jiheong Kang, Daigo Miyajima, Tadashi Mori, Yoshihisa Inoue, Yoshimitsu Itoh, Takuzo Aida

[Report] Termite mounds can increase the robustness of dryland ecosystems to climatic change

Self-organized spatial vegetation patterning is widespread and has been described using models of scale-dependent feedback between plants and water on homogeneous substrates. As rainfall decreases, these models yield a characteristic sequence of patterns with increasingly sparse vegetation, followed by sudden collapse to desert. Thus, the final, spot-like pattern may provide early warning for such catastrophic shifts. In many arid ecosystems, however, termite nests impart substrate heterogeneity by altering soil properties, thereby enhancing plant growth. We show that termite-induced heterogeneity interacts with scale-dependent feedbacks to produce vegetation patterns at different spatial grains. Although the coarse-grained patterning resembles that created by scale-dependent feedback alone, it does not indicate imminent desertification. Rather, mound-field landscapes are more robust to aridity, suggesting that termites may help stabilize ecosystems under global change. Authors: Juan A. Bonachela, Robert M. Pringle, Efrat Sheffer, Tyler C. Coverdale, Jennifer A. Guyton, Kelly K. Caylor, Simon A. Levin, Corina E. Tarnita

[Report] Genetic control of distal stem cell fate within root and embryonic meristems

The root meristem consists of populations of distal and proximal stem cells and an organizing center known as the quiescent center. During embryogenesis, initiation of the root meristem occurs when an asymmetric cell division of the hypophysis forms the distal stem cells and quiescent center. We have identified NO TRANSMITTING TRACT (NTT) and two closely related paralogs as being required for the initiation of the root meristem. All three genes are expressed in the hypophysis, and their expression is dependent on the auxin-signaling pathway. Expression of these genes is necessary for distal stem cell fate within the root meristem, whereas misexpression is sufficient to transform other stem cell populations to a distal stem cell fate in both the embryo and mature roots. Authors: Brian C. W. Crawford, Jared Sewell, Greg Golembeski, Carmel Roshan, Jeff A. Long, Martin F. Yanofsky

[Report] Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology

Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization. Authors: Meaghan Creed, Vincent Jean Pascoli, Christian Lüscher

[Report] Impact of regulatory variation from RNA to protein

The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation. Authors: Alexis Battle, Zia Khan, Sidney H. Wang, Amy Mitrano, Michael J. Ford, Jonathan K. Pritchard, Yoav Gilad

[Report] Inflammation-induced disruption of SCS macrophages impairs B cell responses to secondary infection

The layer of macrophages at the subcapsular sinus (SCS) captures pathogens entering the lymph node, preventing their global dissemination and triggering an immune response. However, how infection affects SCS macrophages remains largely unexplored. Here we show that infection and inflammation disrupt the organization of SCS macrophages in a manner that involves the migration of mature dendritic cells to the lymph node. This disrupted organization reduces the capacity of SCS macrophages to retain and present antigen in a subsequent secondary infection, resulting in diminished B cell responses. Thus, the SCS macrophage layer may act as a sensor or valve during infection to temporarily shut down the lymph node to further antigenic challenge. This shutdown may increase an organism’s susceptibility to secondary infections. Authors: Mauro Gaya, Angelo Castello, Beatriz Montaner, Neil Rogers, Caetano Reis e Sousa, Andreas Bruckbauer, Facundo D. Batista

[Report] Pervasive degeneracy and epistasis in a protein-protein interface

Mapping protein sequence space is a difficult problem that necessitates the analysis of 20N combinations for sequences of length N. We systematically mapped the sequence space of four key residues in the Escherichia coli protein kinase PhoQ that drive recognition of its substrate PhoP. We generated a library containing all 160,000 variants of PhoQ at these positions and used a two-step selection coupled to next-generation sequencing to identify 1659 functional variants. Our results reveal extensive degeneracy in the PhoQ-PhoP interface and epistasis, with the effect of individual substitutions often highly dependent on context. Together, epistasis and the genetic code create a pattern of connectivity of functional variants in sequence space that likely constrains PhoQ evolution. Consequently, the diversity of PhoQ orthologs is substantially lower than that of functional PhoQ variants. Authors: Anna I. Podgornaia, Michael T. Laub