Dynamic control of shape can bring multifunctionality to devices. Soft materials capable of programmable shape change require localized control of the magnitude and directionality of a mechanical response. We report the preparation of soft, ordered materials referred to as liquid crystal elastomers. The direction of molecular order, known as the director, is written within local volume elements (voxels) as small as 0.0005 cubic millimeters. Locally, the director controls the inherent mechanical response (55% strain) within the material. In monoliths with spatially patterned director, thermal or chemical stimuli transform flat sheets into three-dimensional objects through controlled bending and stretching. The programmable mechanical response of these materials could yield monolithic multifunctional devices or serve as reconfigurable substrates for flexible devices in aerospace, medicine, or consumer goods. Authors: Taylor H. Ware, Michael E. McConney, Jeong Jae Wie, Vincent P. Tondiglia, Timothy J. White

The availability of genome sequences from 16 anopheline species provides unprecedented opportunities to study the evolution of reproductive traits relevant for malaria transmission. In Anopheles gambiae, a likely candidate for sexual selection is male 20-hydroxyecdysone (20E). Sexual transfer of this steroid hormone as part of a mating plug dramatically changes female physiological processes intimately tied to vectorial capacity. By combining phenotypic studies with ancestral state reconstructions and phylogenetic analyses, we show that mating plug transfer and male 20E synthesis are both derived characters that have coevolved in anophelines, driving the adaptation of a female 20E-interacting protein that promotes oogenesis via mechanisms also favoring Plasmodium survival. Our data reveal coevolutionary dynamics of reproductive traits between the sexes likely to have shaped the ability of anophelines to transmit malaria. Authors: Sara N. Mitchell, Evdoxia G. Kakani, Adam South, Paul I. Howell, Robert M. Waterhouse, Flaminia Catteruccia

The recent slowdown in global warming has brought into question the reliability of climate model projections of future temperature change and has led to a vigorous debate over whether this slowdown is the result of naturally occurring, internal variability or forcing external to Earth’s climate system. To address these issues, we applied a semi-empirical approach that combines climate observations and model simulations to estimate Atlantic- and Pacific-based internal multidecadal variability (termed “AMO” and “PMO,” respectively). Using this method, the AMO and PMO are found to explain a large proportion of internal variability in Northern Hemisphere mean temperatures. Competition between a modest positive peak in the AMO and a substantially negative-trending PMO are seen to produce a slowdown or “false pause” in warming of the past decade. Authors: Byron A. Steinman, Michael E. Mann, Sonya K. Miller

Double-stranded RNAs (dsRNAs) targeted against essential genes can trigger a lethal RNA interference (RNAi) response in insect pests. The application of this concept in plant protection is hampered by the presence of an endogenous plant RNAi pathway that processes dsRNAs into short interfering RNAs. We found that long dsRNAs can be stably produced in chloroplasts, a cellular compartment that appears to lack an RNAi machinery. When expressed from the chloroplast genome, dsRNAs accumulated to as much as 0.4% of the total cellular RNA. Transplastomic potato plants producing dsRNAs targeted against the β-actin gene of the Colorado potato beetle, a notorious agricultural pest, were protected from herbivory and were lethal to its larvae. Thus, chloroplast expression of long dsRNAs can provide crop protection without chemical pesticides. Authors: Jiang Zhang, Sher Afzal Khan, Claudia Hasse, Stephanie Ruf, David G. Heckel, Ralph Bock

Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy. Authors: Yasuteru Sakurai, Andrey A. Kolokoltsov, Cheng-Chang Chen, Michael W. Tidwell, William E. Bauta, Norbert Klugbauer, Christian Grimm, Christian Wahl-Schott, Martin Biel, Robert A. Davey

The Mesolithic-to-Neolithic transition marked the time when a hunter-gatherer economy gave way to agriculture, coinciding with rising sea levels. Bouldnor Cliff, is a submarine archaeological site off the Isle of Wight in the United Kingdom that has a well-preserved Mesolithic paleosol dated to 8000 years before the present. We analyzed a core obtained from sealed sediments, combining evidence from microgeomorphology and microfossils with sedimentary ancient DNA (sedaDNA) analyses to reconstruct floral and faunal changes during the occupation of this site, before it was submerged. In agreement with palynological analyses, the sedaDNA sequences suggest a mixed habitat of oak forest and herbaceous plants. However, they also provide evidence of wheat 2000 years earlier than mainland Britain and 400 years earlier than proximate European sites. These results suggest that sophisticated social networks linked the Neolithic front in southern Europe to the Mesolithic peoples of northern Europe. Authors: Oliver Smith, Garry Momber, Richard Bates, Paul Garwood, Simon Fitch, Mark Pallen, Vincent Gaffney, Robin G. Allaby

Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N6-methyladenosine (m6A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m6A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m6A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner. Authors: Shay Geula, Sharon Moshitch-Moshkovitz, Dan Dominissini, Abed AlFatah Mansour, Nitzan Kol, Mali Salmon-Divon, Vera Hershkovitz, Eyal Peer, Nofar Mor, Yair S. Manor, Moshe Shay Ben-Haim, Eran Eyal, Sharon Yunger, Yishay Pinto, Diego Adhemar Jaitin, Sergey Viukov, Yoach Rais, Vladislav Krupalnik, Elad Chomsky, Mirie Zerbib, Itay Maza, Yoav Rechavi, Rada Massarwa, Suhair Hanna, Ido Amit, Erez Y. Levanon, Ninette Amariglio, Noam Stern-Ginossar, Noa Novershtern, Gideon Rechavi, Jacob H. Hanna

Reactivation of telomerase, the chromosome end–replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone. Authors: Sumit Borah, Linghe Xi, Arthur J. Zaug, Natasha M. Powell, Garrett M. Dancik, Scott B. Cohen, James C. Costello, Dan Theodorescu, Thomas R. Cech

Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation. Authors: Erik Arner, Carsten O. Daub, Kristoffer Vitting-Seerup, Robin Andersson, Berit Lilje, Finn Drabløs, Andreas Lennartsson, Michelle Rönnerblad, Olga Hrydziuszko, Morana Vitezic, Tom C. Freeman, Ahmad M. N. Alhendi, Peter Arner, Richard Axton, J. Kenneth Baillie, Anthony Beckhouse, Beatrice Bodega, James Briggs, Frank Brombacher, Margaret Davis, Michael Detmar, Anna Ehrlund, Mitsuhiro Endoh, Afsaneh Eslami, Michela Fagiolini, Lynsey Fairbairn, Geoffrey J. Faulkner, Carmelo Ferrai, Malcolm E. Fisher, Lesley Forrester, Daniel Goldowitz, Reto Guler, Thomas Ha, Mitsuko Hara, Meenhard Herlyn, Tomokatsu Ikawa, Chieko Kai, Hiroshi Kawamoto, Levon M. Khachigian, S. Peter Klinken, Soichi Kojima, Haruhiko Koseki, Sarah Klein, Niklas Mejhert, Ken Miyaguchi, Yosuke Mizuno, Mitsuru Morimoto, Kelly J. Morris, Christine Mummery, Yutaka Nakachi, Soichi Ogishima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry Ovchinnikov, Robert Passier, Margaret Patrikakis, Ana Pombo, Xian-Yang Qin, Sugata Roy, Hiroki Sato, Suzana Savvi, Alka Saxena, Anita Schwegmann, Daisuke Sugiyama, Rolf Swoboda, Hiroshi Tanaka, Andru Tomoiu, Louise N. Winteringham, Ernst Wolvetang, Chiyo Yanagi-Mizuochi, Misako Yoneda, Susan Zabierowski, Peter Zhang, Imad Abugessaisa, Nicolas Bertin, Alexander D. Diehl, Shiro Fukuda, Masaaki Furuno, Jayson Harshbarger, Akira Hasegawa, Fumi Hori, Sachi Ishikawa-Kato, Yuri Ishizu, Masayoshi Itoh, Tsugumi Kawashima, Miki Kojima, Naoto Kondo, Marina Lizio, Terrence F. Meehan, Christopher J. Mungall, Mitsuyoshi Murata, Hiromi Nishiyori-Sueki, Serkan Sahin, Sayaka Nagao-Sato, Jessica Severin, Michiel J.L. de Hoon, Jun Kawai, Takeya Kasukawa, Timo Lassmann, Harukazu Suzuki, Hideya Kawaji, Kim M. Summers, Christine Wells, , David A. Hume, Alistair R.R. Forrest, Albin Sandelin, Piero Carninci, Yoshihide Hayashizaki

A central process in evolution is the recruitment of genes to regulatory networks. We engineered immotile strains of the bacterium Pseudomonas fluorescens that lack flagella due to deletion of the regulatory gene fleQ. Under strong selection for motility, these bacteria consistently regained flagella within 96 hours via a two-step evolutionary pathway. Step 1 mutations increase intracellular levels of phosphorylated NtrC, a distant homolog of FleQ, which begins to commandeer control of the fleQ regulon at the cost of disrupting nitrogen uptake and assimilation. Step 2 is a switch-of-function mutation that redirects NtrC away from nitrogen uptake and toward its novel function as a flagellar regulator. Our results demonstrate that natural selection can rapidly rewire regulatory networks in very few, repeatable mutational steps. Authors: Tiffany B. Taylor, Geraldine Mulley, Alexander H. Dills, Abdullah S. Alsohim, Liam J. McGuffin, David J. Studholme, Mark W. Silby, Michael A. Brockhurst, Louise J. Johnson, Robert W. Jackson

Polycomb and Trithorax group proteins encode the epigenetic memory of cellular positional identity by establishing inheritable domains of repressive and active chromatin within the Hox clusters. Here we demonstrate that the CCCTC-binding factor (CTCF) functions to insulate these adjacent yet antagonistic chromatin domains during embryonic stem cell differentiation into cervical motor neurons. Deletion of CTCF binding sites within the Hox clusters results in the expansion of active chromatin into the repressive domain. CTCF functions as an insulator by organizing Hox clusters into spatially disjoint domains. Ablation of CTCF binding disrupts topological boundaries such that caudal Hox genes leave the repressed domain and become subject to transcriptional activation. Hence, CTCF is required to insulate facultative heterochromatin from impinging euchromatin to produce discrete positional identities. Authors: Varun Narendra, Pedro P. Rocha, Disi An, Ramya Raviram, Jane A. Skok, Esteban O. Mazzoni, Danny Reinberg

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On this week's show: sexual traits and malaria transmission in mosquitoes, and a roundup of daily news stories.

A decade ago, the "sink or swim" culture was widespread in research. But academic institutions across the United States and Europe are now investing resources in helping young researchers gain the skills they need for climbing the career ladder. Top on the list are leadership skills, whether for conflict management, handling finances, or negotiating intellectual property rights in an international consortium, these are highly rated assets that can help researchers advance to senior roles. Here's a look at some of the most established leadership programs that hold alumni who are leaping ahead as a result of the training.Read the Feature (Full-Text HTML)Read the Feature (PDF) Author: Julie Clayton

Among the various ways of thinking and knowing about the universe and ourselves, science is special. Asking questions that can be answered empirically and engaging in open communication so that others can collectively review and verify possible answers lead to the most reliable knowledge—a knowledge that is powerfully applicable in daily life. Science is, as physician and essayist Lewis Thomas wrote, the “shrewdest maneuver” for discovering the world. This grand and clever enterprise, while surely not removing all worldly woes, brings beauty, wonderfully fulfilling intellectual pleasure, and cultural enrichment. It can lead to improved human interaction, more constructive commerce, and a better quality of life. Science helps bring what I think is a deep human need—a sense of progress. Author: Rush D. Holt

In science news around the world, fracking gets a boost in the United Kingdom, genetic analyses reveal that a gray wolf seen at the north rim of the Grand Canyon in 2014 and hailed as a sign of the success of conservation efforts was shot by a hunter later that year, Japan's RIKEN laboratories announce punishments for staff embroiled in a stem cell scandal, a gap in weather satellite coverage looms for the United States, and a Brazil-based researcher sues a journal over potential retractions of his papers. Also, the movie Interstellar inspires new insights into black holes. And the long fluttering tails of luna moth wings confuse hungry bats.

Driven by a mysterious atmospheric anomaly, a 2-year-long drought has triggered a crippling water crisis in southeast Brazil, a region of 85 million people that includes the nation's biggest metropolis, São Paulo. The São Paulo government has reduced the water pressure in its mains, which regularly leaves faucets running dry. And it is now taking a carrot-and-stick approach to water usage, financially rewarding those who conserve and fining those who waste. Barring a sudden reversal of meteorological misfortune, officials are contemplating drastic rationing that would deprive millions of households of water for up to 5 days a week. In a press conference last week, the Brazilian Academy of Sciences took state authorities to task for failing to take bolder actions sooner and for a lack of transparency about the gravity of the situation. Author: Herton Escobar

It is the largest body in the asteroid belt, yet Ceres is not an asteroid. Nor is it a planet. Ceres is a dwarf planet, and like its more famous cousin in the outer solar system, Pluto, Ceres harbors a lot of ice. This has astrobiologists salivating at the arrival of NASA's Dawn spacecraft, which will begin orbiting Ceres on 6 March. Scientists suspect that Ceres was massive enough for its rock and ice to separate into layers. There is evidence that Ceres's icy mantle was once a watery subterranean ocean, and there are hints that this liquid may remain even today. Dawn will map the surface, seeking evidence that this liquid occasionally erupted at that surface. Author: Eric Hand

Despite their allegiances to 47 different nations, 87 ethnic groups, and countless football teams, Europeans have a lot in common. Most speak closely related languages that are members of the great Indo-European language family. A new study uses ancient DNA to suggest that a massive migration of herders from the east shaped the genomes of most living Europeans—and that these immigrants may have been the source of Proto-Indo-European (PIE), the mysterious ancestral tongue from which the more than 400 Indo-European languages sprang. Based on DNA gathered from dozens of ancient skeletons, the study,​ described last week in a preprint posted on the bioRxiv server, reveals when and where different groups of people arrived in Europe and interbred with each other. One surprise is that a migration of herders from the steppes of today's Russia and Ukraine about 4500 years ago significantly shifted the genetic makeup of today's Europeans. Many living Europeans retain traces of this influx, which the authors link to an ancient culture of steppe herders known as the Yamnaya. The team behind the study further suggests that the Yamnaya people spoke either PIE or an early form of Indo-European language and brought it to central Europe, coming down on one side of a long-standing debate about the origins of PIE. That idea is supported by a second paper published this week in Language, which uses changes in words instead of genes to claim that the steppelands were the likely homeland for the origins of many Indo-European languages. But some researchers aren't convinced and ​say the genetic ​data aren't strong enough to connect ancient people known by their DNA to any particular language. Authors: Michael Balter, Ann Gibbons

As part of his proposed precision medicine initiative, President Barack Obama has called for enlisting at least 1 million American volunteers in a long-term study of genes, environment, and health. The idea is to mine all kinds of information, from participants' DNA and medical records to their physical activity tracked by Fitbits, to accelerate the development of treatments tailored to individual patients. It may sound straightforward, but not so, concluded nearly 90 scientists and company, industry, and patient representatives who met at the National Institutes of Health last week to begin planning this massive U.S. cohort study. Still, by the end of the 2-day meeting, most of the participants seemed enthusiastically on board, if somewhat daunted by the challenges of designing a project that could cost a billion dollars or more and last a decade or longer. Author: Jocelyn Kaiser

Against the backdrop of "Snowmageddon" and other powerful winter storms that have blasted the United States, Europe, and Asia in the past few years, a different kind of tempest has been swirling within the Arctic science community. Its core is a flurry of recent research proposing that such extreme weather events in the midlatitudes are linked through the atmosphere with the effects of rapid climate change in the Arctic, such as dwindling sea ice. The idea has galvanized the public and even caught the attention of the White House. But some Arctic researchers say the data don't support it—or that the jury is at least still out. Now, scientists are tackling the issue in earnest, and an increasing number of conferences and workshops are bringing together scientists with a range of viewpoints on this issue, in hopes that a coordinated effort will measure the reach of the north. Author: Carolyn Gramling

Climate scientist Judah Cohen envisions a series of causal links between how much snow falls over Siberia each October and weather patterns in the midlatitudes. Siberian snow cover, he says, has been increasing over the past 2 decades. His "six-step" cycle, which progresses from snow cover in Siberia to the breakdown of the stratospheric polar vortex and a more meandering jet stream, also has room for melting sea ice, he says—and he notes that he has successfully used this series of links to predict changes in the polar vortex, including the powerful winter storms of early 2015 in the northeastern United States. But not everyone concurs that snow cover is the silver bullet—or with Cohen's observation that snow cover over Siberia has been on the rise. Author: Carolyn Gramling

The species assemblages that make up ecological communities change over time (1), in part as a result of interactions among species such as predation and competition. However, it is often not clear how interactions among individuals scale up to affect broader ecological processes such as changes in species assemblages (2, 3). On page 875 of this issue, Duckworth et al. (4) provide field evidence for how individual competition between members of different bird species leads to changes in community composition. The key to these observations lies in maternal hormone changes that affect their sons' behavioral characteristics. Author: Ben Dantzer

Skin cancer is the most prevalent form of cancer, with a lifetime risk of 1 in 5 for Americans (1). Most skin cancers can be attributed to C→T and CC→TT mutations in DNA resulting from cyclobutane pyrimidine dimers (CPDs) produced by the direct absorption of UVB light (290 to 320 nm) present in sunlight (2). The most generally accepted mechanism for the formation of these mutations is that Cs or 5-methyl-Cs in the CPDs rapidly deaminate to Us or Ts, which are then replicated in an error-free manner. One might expect that photodamage would cease once out of the Sun, but Premi et al., on page 842 of this issue, show that this is not the case in melanocytes (3). A substantial fraction of UV damage to DNA in these cells may be occurring in the dark, by a novel pathway with important implications for melanoma formation. Author: John-Stephen Taylor

The U.S. Centers for Disease Control and Prevention estimates the prevalence of autism spectrum disorders (ASDs) to be 1 in 68 children in the United States, yet no drugs to treat the debilitating social deficits of ASD are available. Oxytocin, a natural brain peptide produced in the hypothalamus, has received considerable attention as a potential treatment for social deficits in ASD. Acute intranasal oxytocin temporarily enhances social cognition, empathy, and reciprocity in individuals with ASD (1). However, recent clinical trials have yielded mixed results, leaving the field questioning whether oxytocin can live up to the hype. Authors: Larry J. Young, Catherine E. Barrett

Cells need to find ways of surviving when times are hard. One way of dealing with nutrient scarcity is to digest intracellular constituents, providing a source of amino acids that can be used to synthesize proteins that are essential for survival (1). This process of autophagy (2), however, poses a problem for the body's specialized fuel-sensing cells. β cells within the pancreatic islet respond to blood glucose concentration—when it rises after a meal, these cells release insulin; otherwise, under basal conditions (between meals), the cells are in a “starvation”-like state (3). So how do they maintain a normal turnover of intracellular components during this metabolic deprivation? Why don't they eat themselves as other cells would? At the very least, autophagy under basal conditions could compromise the ability to respond optimally to fluctuations in blood glucose, posing a health risk. On page 878 of this issue, Goginashvili et al. (4) show how β cells avoid inappropriate autophagy, and describe a form of this process tailored to the needs of these cells. Author: Guy A. Rutter

Light may behave both as a particle and as a wave. Newton conjectured the particle aspects and observed wave aspects (“Newton's rings”). Young showed wave interference in his double-slit experiments, and Einstein formulated light as particles (photons) to explain the photoelectric effect. This dual description leads to two different speeds for light: the wave speed, which for a plane wave in vacuum is the now fixed constant, c; and the particle or “group” speed at which energy or information propagates, which can be less than c—even zero, in some cases. On page 857 of this issue, Giovannini et al. (1) convincingly show that individual photons can have a speed less than c. In order to show this, the individual photons were prepared with transverse structure, so they cannot be represented as truly plane waves. Author: J. R. Sambles

The description of the potential energy surface of a single bond rotation is a standard concept for understanding chemical reactions and molecular motions (1). The energetic progression around a single bond in biphenyl (see the first figure) (2) provides an illustration. An entire conformational energy landscape can be captured with a simple reaction coordinate diagram or multidimensional potential energy surface (3). On page 863 of this issue, Pearson et al. describe a way to trap and observe an otherwise fleeting state at a rarified elevation of the conformational energy landscape (4). Authors: David K. Romney, Scott J. Miller

Large areas of the United States long considered geologically stable with little or no detected seismicity have recently become seismically active. The increase in earthquake activity began in the mid-continent starting in 2001 (1) and has continued to rise. In 2014, the rate of occurrence of earthquakes with magnitudes (M) of 3 and greater in Oklahoma exceeded that in California (see the figure). This elevated activity includes larger earthquakes, several with M > 5, that have caused significant damage (2, 3). To a large extent, the increasing rate of earthquakes in the mid-continent is due to fluid-injection activities used in modern energy production (1, 4, 5). We explore potential avenues for mitigating effects of induced seismicity. Although the United States is our focus here, Canada, China, the UK, and others confront similar problems associated with oil and gas production, whereas quakes induced by geothermal activities affect Switzerland, Germany, and others. Authors: A. McGarr, B. Bekins, N. Burkardt, J. Dewey, P. Earle, W. Ellsworth, S. Ge, S. Hickman, A. Holland, E. Majer, J. Rubinstein, A. Sheehan

Microorganisms may offer unique insights into the nature and evolution of life Author: Adrian Woolfson