The 1918 flu, 100 years later Science (IF 37.205) Pub Date : 2018-01-19 Jessica A. Belser, Terrence M. Tumpey
Combating a disease of unknown cause is a daunting task. One hundred years ago, a pandemic of poorly understood etiology and transmissibility spread worldwide, causing an estimated 50 million deaths. Initially attributed to Haemophilus influenzae, it was not until the 1930s that an H1 subtype was identified as the causative strain. Subsequent influenza pandemics in 1957, 1968, and 2009 did not approach levels of morbidity and mortality comparable to those of the 1918 “Spanish flu,” leaving unanswered for almost a century questions regarding the extraordinary virulence and transmissibility of this unique strain. Technological advances made reconstruction of the 1918 virus possible; now, continued research, vaccine development, and preparedness are essential to ensure that such a devastating public health event is not repeated.
News at a glance Science (IF 37.205) Pub Date : 2018-01-19 American Association for the Advancement of Science
In science news around the world, University College London investigates a controversial, low-profile conference on the genetics of intelligence, and the U.S. Environmental Protection Agency curtails the amount of information it releases on preliminary assessments of potentially hazardous new chemicals or new uses of existing chemicals. The pending completion of a new highway through the Brazilian Amazon is alarming tropical ecologists, who fear it will open the way to increased habitat destruction. Two political parties in Germany working to form a coalition government pledged to raise spending on R&D to 3.5% of gross domestic product until 2025, which would be among the highest rates in the world. And a study reports that biomedical research papers with multiple authors more often list men as the first author, even when the male and female authors are noted as contributing equally.
Newborn exoplanet eyed for moons and rings Science (IF 37.205) Pub Date : 2018-01-19 Daniel Clery
Astronomers are staring at a nearby star in hopes of seeing a giant baby of a planet—perhaps accompanied by dust clouds, rings, or newborn moons—pass across its face. Last week, the newest and tiniest telescope joined the vigil, when the French-built PicSat rode into orbit on an Indian rocket. It will be able to continuously monitor the star, β Pictoris, until chances of seeing the once-in-20-year transit event diminish in a few months' time. Astronomers are fascinated by β Pictoris, a bright star just 63 light-years away, because it is a natural laboratory for how solar systems form given its age of only 24 million years—an infant in stellar terms.
‘Liquid biopsy’ for cancer promises early detection Science (IF 37.205) Pub Date : 2018-01-19 Jocelyn Kaiser
A team of researchers has taken a major step toward one of the hottest goals in cancer research: a blood test that can detect tumors early. Their new test, which examines cancer-related DNA and proteins in the blood, yielded a positive result about 70% of the time across eight common cancer types in 1005 patients whose tumors had not yet spread—among the best performances yet for a universal cancer blood test. It also narrowed down the form of cancer. The work, reported online today in Science, could one day lead to a tool for routinely screening people and catching tumors before they cause symptoms, when chances are best for a cure.
Tamed immune reaction aids pregnancy Science (IF 37.205) Pub Date : 2018-01-19 Elizabeth Pennisi
The riskiest moment in any human pregnancy is arguably when the fertilized egg attaches to the womb wall and tries to establish a lifeline between embryo and mother. About half of in vitro pregnancies fail during this implantation stage, and many natural pregnancies end then as well. Now, researchers comparing pregnancy in opossums and several other mammals have shown how precise control of an immune process, inflammation, is critical to success or failure. In work reported at the annual meeting of the Society for Integrative and Comparative Biology in San Francisco, California, a Yale University team found that so-called placental mammals have tweaked an ancient inflammatory process to enable embryos to implant and persist in the womb. Placental mammals—named for the mass of tissue in the uterus that serves as the interface between mother and fetus—have specialized uterine cells that suppress the release of a key immune-stimulating molecule. This suppression may help delay the rejection of the embryo until it's fully developed, they reported.
Tensions flare over electric fishing in European waters Science (IF 37.205) Pub Date : 2018-01-19 Erik Stokstad
In a surprise outcome, the European Parliament voted 16 January to ban a type of electric fishing that has demonstrated environmental benefits, as part of legislation to reform Europe's fisheries. The proposed end to "pulse trawling"—in which short bursts of electricity get flatfish out of the sediment and into nets—is a major disappointment to Dutch fishing companies, which have invested heavily in the technology; they claim it is less damaging to marine ecosystems than traditional bottom trawling and saves energy. But fishing groups in other EU countries are increasingly angry about competition from the Dutch pulse trawlers. And a coalition of environmental organizations worries about harm to nontarget marine life. Other nongovernmental organizations say pulse trawling has promise to reduce environmental impacts and that ending it now would penalize the fishing industry for innovating. The vote is just the first step in negotiations with the European Commission and member states over the large package of fisheries reforms.
Rochester roiled by fallout from sexual harassment case Science (IF 37.205) Pub Date : 2018-01-19 Meredith Wadman
The University of Rochester (U of R) in New York struggled last week to respond to its president's sudden departure even as a lengthy report was issued that largely approved of his administration's handling of explosive sexual harassment complaints against a noted linguist. President Joel Seligman said on 11 January that he will leave U of R on 28 February, an exit he declared to be "in the best interests of the University." The university and its highly esteemed Department of Brain and Cognitive Sciences (BCS) have been buffeted by protests since September 2017, when complaints about alleged sexual harassment by BCS professor T. Florian Jaeger, and the university's handling of them, became public. Last week's report, by former U.S. attorney Mary Jo White of the Debevoise & Plimpton law firm in New York City, concluded that Jaeger, who had multiple consensual relationships with current, former, or prospective students, did not sexually harass any woman or breach then-existing university policies on relationships with students. But the university, its president, and its provost, Robert Clark, must still contend with a lawsuit filed in federal court last month by seven current and former BCS professors, a former postdoc, and a former graduate student. They allege that university administrators permitted Jaeger to create a hostile environment based on sex and retaliated against them after they complained.
Are algorithms good judges? Science (IF 37.205) Pub Date : 2018-01-19 Catherine Matacic
Every day, judges across the United States face an important decision: Should they jail a defendant awaiting trial—whose innocence or guilt has not yet been determined—or should they release the person on bail back into the community, where they might commit a crime? Increasingly, courts are turning to computer-based tools to help make those decisions, lured by the promise of complex algorithms that use an array of factors to spit out risk scores. But a new study suggests that at least one widely used algorithm produces risk assessments that are no better than those reached by online volunteers given just a few key pieces of information about a defendant.
The believer Science (IF 37.205) Pub Date : 2018-01-19 Lizzie Wade
According to the Book of Mormon, ancient people called the Nephites sailed from Israel to the Americas around 600 B.C.E. Centuries later, Jesus appeared to them after his resurrection. Thomas Stuart Ferguson, a Mormon lawyer from California, was determined to use science to prove these scriptures true. He and other Mormons were certain that these events had happened in the ancient Americas, but debates raged over exactly how their sacred lands mapped onto real-world geography. After years of studying maps, Mormon scripture, and Spanish chronicles, Ferguson concluded that the Book of Mormon took place around the Isthmus of Tehuantepec, the narrowest part of Mexico. He went on to found an organization that supported archaeological excavations in southern Mexico, opening an important new window on Mesoamerica's past. His quest eventually spurred expeditions that unearthed traces of the region's earliest complex societies and explored an unstudied area that turned out to be a crucial cultural crossroads. Even today, the institute Ferguson founded hums with research. But proof of Mormon beliefs eluded him. His mission led him further and further from his faith, eventually sapping him of religious conviction entirely. Ferguson placed his faith in the hands of science, not realizing they were the lion's jaws.
Assessing nature's contributions to people Science (IF 37.205) Pub Date : 2018-01-19 Sandra Díaz, Unai Pascual, Marie Stenseke, Berta Martín-López, Robert T. Watson, Zsolt Molnár, Rosemary Hill, Kai M. A. Chan, Ivar A. Baste, Kate A. Brauman, Stephen Polasky, Andrew Church, Mark Lonsdale, Anne Larigauderie, Paul W. Leadley, Alexander P. E. van Oudenhoven, Felice van der Plaat, Matthias Schröter, Sandra Lavorel, Yildiz Aumeeruddy-Thomas, Elena Bukvareva, Kirsten Davies, Sebsebe Demissew, Gunay Erpul, Pierre Failler, Carlos A. Guerra, Chad L. Hewitt, Hans Keune, Sarah Lindley, Yoshihisa Shirayama
A major challenge today and into the future is to maintain or enhance beneficial contributions of nature to a good quality of life for all people. This is among the key motivations of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), a joint global effort by governments, academia, and civil society to assess and promote knowledge of Earth's biodiversity and ecosystems and their contribution to human societies in order to inform policy formulation. One of the more recent key elements of the IPBES conceptual framework (1) is the notion of nature's contributions to people (NCP), which builds on the ecosystem service concept popularized by the Millennium Ecosystem Assessment (MA) (2). But as we detail below, NCP as defined and put into practice in IPBES differs from earlier work in several important ways. First, the NCP approach recognizes the central and pervasive role that culture plays in defining all links between people and nature. Second, use of NCP elevates, emphasizes, and operationalizes the role of indigenous and local knowledge in understanding nature's contribution to people.
The art of manufacturing molecules Science (IF 37.205) Pub Date : 2018-01-19 Christian H. Hornung
The way we manufacture many of the products used in everyday life, such as the ingredients in shampoo, the plastic components of smartphones, the vitamins and pharmaceuticals we take, and the packaging that all of them come in, has not changed in a significant way over the last hundred years. Arguably, these methods of manufacturing are even older and were already applied in the first large-scale chemical processes in the 19th century, in which new products such as vulcanized rubber, synthetic dyes, or industrial fertilizers were first produced on scales unknown to society at the time. The development of these industrial processes was driven by the benefits of economy of scale, with the aim of centralizing, optimizing, maximizing, and integrating production. In recent years, efforts were made by a series of research groups to reverse this trend and decentralize, miniaturize, and even digitize chemical manufacturing. On page 314 of this issue, Kitson et al. (1) report the synthesis of active pharmaceutical ingredients (APIs) on demand in a three-dimensional (3D)-printed, miniaturized reactor cascade. A complete multistep synthesis of the muscle relaxant baclofen was developed and digitized for remote bench-scale manufacture.
Quantum liquids get thin Science (IF 37.205) Pub Date : 2018-01-19 Igor Ferrier-Barbut, Tilman Pfau
A liquid exists when interactions that attract its constituent particles to each other are counterbalanced by a repulsion acting at higher densities. Other characteristics of liquids are short-range correlations and the existence of surface tension (1). Ultracold atom experiments provide a privileged platform with which to observe exotic states of matter, but the densities are far too low to obtain a conventional liquid because the atoms are too far apart to create repulsive forces arising from the Pauli exclusion principle of the atoms' internal electrons. The observation of quantum liquid droplets in an ultracold mixture of two quantum fluids is now reported on page 301 of this issue by Cabrera et al. (2) and a recent preprint by Semeghini et al. (3). Unlike conventional liquids, these liquids arise from a weak attraction and repulsive many-body correlations in the mixtures.
A bacterial coat that is not pure cotton Science (IF 37.205) Pub Date : 2018-01-19 Michael Y. Galperin, Daria N. Shalaeva
Cellulose, a linear polymer of glucose residues, is the main component of plant cell walls and the most abundant biomolecule on the planet. Cellulose fibers from wood, cotton, and linen are mostly used as such, but can also be chemically modified to make rayon, viscose, and other textiles. Many bacteria also synthesize cellulose. Cellulose fibers produced by the model organism Komagataeibacter (Gluconacetobacter) xylinus are very similar to those found in plants (1) and are increasingly used in biotechnology and nanotechnology (2, 3). Escherichia coli and many other bacteria produce cellulose as a key component of the extracellular matrix that coats the cells to form a biofilm, a complex multicellular community consisting of numerous bacteria, exopolysaccharides (like cellulose), protein fibers, and DNA (4–6). The cellulose in biofilms was assumed to be the same as that produced by G. xylinus, owing to the same pattern of staining with Congo red dye and the same cellulose synthase enzyme (4–6). However, on page 334 of this issue, Thongsomboon et al. (7) report that E. coli and Salmonella enterica serovar Typhimurium produce modified cellulose, in which every other glucosyl residue carries an additional phosphoethanolamine (pEtN) group. These findings have important implications for a wide variety of disciplines, from microbiology to materials science.
Taking down defenses to improve vaccines Science (IF 37.205) Pub Date : 2018-01-19 John R. Teijaro, Dennis R. Burton
Vaccines have been spectacularly successful in durable protection against a range of pathogens. However, they have been less successful against pathogens that have evolved immune escape mechanisms (1). For example, the influenza virus surface glycoprotein hemagglutinin (HA), which is the main target (antigen) for protective antibodies, shows enormous sequence diversity between different strains, meaning that antibodies induced by immune responses to one strain of the virus tend to be either inefficient or ineffective against other strains. This observation is often associated with the need for a new influenza vaccine every year. However, the escape mechanisms of influenza virus extend beyond antigenic variation of surface proteins. For example, wild-type viruses typically encountered in natural infection can suppress the host type I interferon (IFN-I) response, which provides the first line of defense against viral infections and promotes stimulation of an optimal immune response (2). On page 290 of this issue, Du et al. (3) describe the generation of a variant influenza virus that, in contrast to the wild type, is hyper-interferon-sensitive (HIS) and therefore attenuated (reduced in virulence). Attenuated viruses typically have lower immune responses than their wild-type counterparts but, in this case, the level of attenuation still resulted in robust immune responses. The authors propose that the HIS approach could form the basis for a more effective influenza vaccine.
Remote control of nanoscale devices Science (IF 37.205) Pub Date : 2018-01-19 Björn Högberg
Processes that occur at the nanometer scale have a tremendous impact on our daily lives. Sophisticated evolved nanomachines operate in each of our cells; we also, as a society, increasingly rely on synthetic nanodevices for communication and computation. Scientists are still only beginning to master this scale, but, recently, DNA nanotechnology (1)—in particular, DNA origami (2)—has emerged as a powerful tool to build structures precise enough to help us do so. On page 296 of this issue, Kopperger et al. (3) show that they are now also able to control the motion of a DNA origami device from the outside by applying electric fields.
Ben Barres (1954–2017) Science (IF 37.205) Pub Date : 2018-01-19 Martin Raff
Ben Barres transformed our understanding of brain glial cells. He lived an extraordinary life and died too young after a 2-year battle with pancreatic cancer. From early childhood, he suffered greatly from gender dysphoria, until transitioning from Barbara to Ben at age 43. This provided enormous relief, as well as rare insight into how differently females and males are treated, fueling a passionate intolerance to prejudice. He was the first openly transgender person elected to the U.S. National Academy of Sciences.
Quarks, culture, combogenesis Science (IF 37.205) Pub Date : 2018-01-19 Barry Wood
The value of Tyler Volk’s Quarks to Culture is evident when the book is placed against popular histories of the universe, dozens of which have provided evidence for an immense cosmic past. But such histories are often anecdotal, like early British histories of the kings of England. Unlike these works, Volk artfully presents the case for structural continuity and systematic creativity across 13.8 billion years of cosmic history.
Enrico Fermi, flaws and all Science (IF 37.205) Pub Date : 2018-01-19 Megan Formato
With the title The Last Man Who Knew Everything and a first chapter entitled “Prodigy,” a reader could be forgiven for expecting David Schwartz’s new biography of Enrico Fermi to be a straightforward hagiography. Luckily, Schwartz’s ambitions are not as simple as providing yet another account of a great man of 20th-century physics. He has other, thornier questions in mind, some of which he credibly addresses and others that he handles less convincingly.
Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design Science (IF 37.205) Pub Date : 2018-01-19 Yushen Du, Li Xin, Yuan Shi, Tian-Hao Zhang, Nicholas C. Wu, Lei Dai, Danyang Gong, Gurpreet Brar, Sara Shu, Jiadi Luo, William Reiley, Yen-Wen Tseng, Hongyan Bai, Ting-Ting Wu, Jieru Wang, Yuelong Shu, Ren Sun
In conventional attenuated viral vaccines, immunogenicity is often suboptimal. Here we present a systematic approach for vaccine development that eliminates interferon (IFN)–modulating functions genome-wide while maintaining virus replication fitness. We applied a quantitative high-throughput genomics system to influenza A virus that simultaneously measured the replication fitness and IFN sensitivity of mutations across the entire genome. By incorporating eight IFN-sensitive mutations, we generated a hyper–interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. Our approach, which attenuates the virus and promotes immune responses concurrently, is broadly applicable for vaccine development against other pathogens.
A self-assembled nanoscale robotic arm controlled by electric fields Science (IF 37.205) Pub Date : 2018-01-19 Enzo Kopperger, Jonathan List, Sushi Madhira, Florian Rothfischer, Don C. Lamb, Friedrich C. Simmel
The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer–by–55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.
Quantum liquid droplets in a mixture of Bose-Einstein condensates Science (IF 37.205) Pub Date : 2018-01-19 C. R. Cabrera, L. Tanzi, J. Sanz, B. Naylor, P. Thomas, P. Cheiney, L. Tarruell
Quantum droplets are small clusters of atoms self-bound by the balance of attractive and repulsive forces. Here, we report on the observation of droplets solely stabilized by contact interactions in a mixture of two Bose-Einstein condensates. We demonstrate that they are several orders of magnitude more dilute than liquid helium by directly measuring their size and density via in situ imaging. We show that the droplets are stablized against collapse by quantum fluctuations and that they require a minimum atom number to be stable. Below that number, quantum pressure drives a liquid-to-gas transition that we map out as a function of interaction strength. These ultradilute isotropic liquids remain weakly interacting and constitute an ideal platform to benchmark quantum many-body theories.
Hydraulic fracturing volume is associated with induced earthquake productivity in the Duvernay play Science (IF 37.205) Pub Date : 2018-01-19 R. Schultz, G. Atkinson, D. W. Eaton, Y. J. Gu, H. Kao
A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (104 to 105 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index–modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.
Chiromagnetic nanoparticles and gels Science (IF 37.205) Pub Date : 2018-01-19 Jihyeon Yeom, Uallisson S. Santos, Mahshid Chekini, Minjeong Cha, André F. de Moura, Nicholas A. Kotov
Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.
Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals Science (IF 37.205) Pub Date : 2018-01-19 Philip J. Kitson, Guillaume Marie, Jean-Patrick Francoia, Sergey S. Zalesskiy, Ralph C. Sigerson, Jennifer S. Mathieson, Leroy Cronin
Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.
A global atlas of the dominant bacteria found in soil Science (IF 37.205) Pub Date : 2018-01-19 Manuel Delgado-Baquerizo, Angela M. Oliverio, Tess E. Brewer, Alberto Benavent-González, David J. Eldridge, Richard D. Bardgett, Fernando T. Maestre, Brajesh K. Singh, Noah Fierer
The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a “most wanted” list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.
Improving refugee integration through data-driven algorithmic assignment Science (IF 37.205) Pub Date : 2018-01-19 Kirk Bansak, Jeremy Ferwerda, Jens Hainmueller, Andrea Dillon, Dominik Hangartner, Duncan Lawrence, Jeremy Weinstein
Developed democracies are settling an increased number of refugees, many of whom face challenges integrating into host societies. We developed a flexible data-driven algorithm that assigns refugees across resettlement locations to improve integration outcomes. The algorithm uses a combination of supervised machine learning and optimal matching to discover and leverage synergies between refugee characteristics and resettlement sites. The algorithm was tested on historical registry data from two countries with different assignment regimes and refugee populations, the United States and Switzerland. Our approach led to gains of roughly 40 to 70%, on average, in refugees’ employment outcomes relative to current assignment practices. This approach can provide governments with a practical and cost-efficient policy tool that can be immediately implemented within existing institutional structures.
Dicer uses distinct modules for recognizing dsRNA termini Science (IF 37.205) Pub Date : 2018-01-19 Niladri K. Sinha, Janet Iwasa, Peter S. Shen, Brenda L. Bass
Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3′ overhanging termini are cleaved distributively. To understand this discrimination, we used cryo–electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3′ overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate–dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers.
Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose Science (IF 37.205) Pub Date : 2018-01-19 Wiriya Thongsomboon, Diego O. Serra, Alexandra Possling, Chris Hadjineophytou, Regine Hengge, Lynette Cegelski
Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that Escherichia coli produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway. The bcsEFG operon is present in many bacteria, including Salmonella species, that also produce the modified cellulose. The discovery of phosphoethanolamine cellulose and the genetic and molecular basis for its production offers opportunities to modulate its production in bacteria and inspires efforts to biosynthetically engineer alternatively modified cellulosic materials.
Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N Science (IF 37.205) Pub Date : 2018-01-19 Sagar Chittori, Jingjun Hong, Hayden Saunders, Hanqiao Feng, Rodolfo Ghirlando, Alexander E. Kelly, Yawen Bai, Sriram Subramaniam
Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo–electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.
Multiplexed gene synthesis in emulsions for exploring protein functional landscapes Science (IF 37.205) Pub Date : 2018-01-19 Calin Plesa, Angus M. Sidore, Nathan B. Lubock, Di Zhang, Sriram Kosuri
Improving our ability to construct and functionally characterize DNA sequences would broadly accelerate progress in biology. Here, we introduce DropSynth, a scalable, low-cost method to build thousands of defined gene-length constructs in a pooled (multiplexed) manner. DropSynth uses a library of barcoded beads that pull down the oligonucleotides necessary for a gene’s assembly, which are then processed and assembled in water-in-oil emulsions. We used DropSynth to successfully build more than 7000 synthetic genes that encode phylogenetically diverse homologs of two essential genes in Escherichia coli. We tested the ability of phosphopantetheine adenylyltransferase homologs to complement a knockout E. coli strain in multiplex, revealing core functional motifs and reasons underlying homolog incompatibility. DropSynth coupled with multiplexed functional assays allows us to rationally explore sequence-function relationships at an unprecedented scale.
AAAS 2018 Annual Meeting Program Science (IF 37.205) Pub Date : 2018-01-19 American Association for the Advancement of Science
This issue of Science includes the program of the 2018 AAAS Annual Meeting. The theme of the AAAS Annual Meeting in Austin, TX, 15 to 19 February 2018, is Advancing Science: Discovery to Application. A PDF of the program as it appears in this issue is available here; for more information on the meeting (including registration forms and information on accommodations), please visit www.aaas.org/meetings/.
Toward dynamic structural biology: Two decades of single-molecule Förster resonance energy transfer Science (IF 37.205) Pub Date : 2018-01-19 Eitan Lerner, Thorben Cordes, Antonino Ingargiola, Yazan Alhadid, SangYoon Chung, Xavier Michalet, Shimon Weiss
Classical structural biology can only provide static snapshots of biomacromolecules. Single-molecule Förster resonance energy transfer (smFRET) paved the way for studying dynamics in macromolecular structures under biologically relevant conditions. Since its first implementation in 1996, smFRET experiments have confirmed previously hypothesized mechanisms and provided new insights into many fundamental biological processes, such as DNA maintenance and repair, transcription, translation, and membrane transport. We review 22 years of contributions of smFRET to our understanding of basic mechanisms in biochemistry, molecular biology, and structural biology. Additionally, building on current state-of-the-art implementations of smFRET, we highlight possible future directions for smFRET in applications such as biosensing, high-throughput screening, and molecular diagnostics.
Membrane protein insertion through a mitochondrial β-barrel gate Science (IF 37.205) Pub Date : 2018-01-19 Alexandra I. C. Höhr, Caroline Lindau, Christophe Wirth, Jian Qiu, David A. Stroud, Stephan Kutik, Bernard Guiard, Carola Hunte, Thomas Becker, Nikolaus Pfanner, Nils Wiedemann
The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop, and inserts into the lateral gate by β-signal exchange. Transport through the Omp85-channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of β-barrel proteins.
Structures of human PRC2 with its cofactors AEBP2 and JARID2 Science (IF 37.205) Pub Date : 2018-01-18 Vignesh Kasinath, Marco Faini, Simon Poepsel, Dvir Reif, Xinyu Ashlee Feng, Goran Stjepanovic, Ruedi Aebersold, Eva Nogales
Transcriptionally repressive histone H3K27 methylation by PRC2 (Polycomb repressive complex 2) is essential for cellular differentiation and development. Here we report cryo-EM structures of human PRC2 in two distinct, active states, while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, while AEBP2 interacts with the RBAP48 subunit mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails and RNA.
Defining the physiological role of SRP in protein-targeting efficiency and specificity Science (IF 37.205) Pub Date : 2018-01-18 Elizabeth A. Costa, Kelly Subramanian, Jodi Nunnari, Jonathan S. Weissman
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP’s in vivo function in yeast. Despite the classic view that SRP recognizes N-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the N terminus. By contrast, many proteins containing cleavable N-terminal signal peptides were efficiently cotranslationally targeted in SRP’s absence. We also revealed an unanticipated consequence of SRP loss: Normally ER-targeted transcripts were mistargeted to mitochondria, leading to mitochondrial defects. These results elucidate SRP’s essential roles in maintaining the efficiency and specificity of protein targeting.
Detection and localization of surgically resectable cancers with a multi-analyte blood test Science (IF 37.205) Pub Date : 2018-01-18 Joshua D. Cohen, Lu Li, Yuxuan Wang, Christopher Thoburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar A. Javed, Fay Wong, Austin Mattox, Ralph. H. Hruban, Christopher L. Wolfgang, Michael G. Goggins, Marco Dal Molin, Tian-Li Wang, Richard Roden, Alison P. Klein, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Silliman, Maria Popoli, Joshua T. Vogelstein, James D. Browne, Robert E. Schoen, Randall E. Brand, Jeanne Tie, Peter Gibbs, Hui-Li Wong, Aaron S. Mansfield, Jin Jen, Samir M. Hanash, Massimo Falconi, Peter J. Allen, Shibin Zhou, Chetan Bettegowda, Luis Diaz, Cristian Tomasetti, Kenneth W. Kinzler, Bert Vogelstein, Anne Marie Lennon, Nickolas Papadopoulos
Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was > 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.
Building superlattices from individual nanoparticles via template-confined DNA-mediated assembly Science (IF 37.205) Pub Date : 2018-01-18 Qing-Yuan Lin, Jarad A. Mason, Zhongyang Li, Wenjie Zhou, Matthew N. O’Brien, Keith A. Brown, Matthew R. Jones, Serkan Butun, Byeongdu Lee, Vinayak P. Dravid, Koray Aydin, Chad A. Mirkin
DNA programmable assembly has been combined with top-down lithography to construct superlattices of discrete, reconfigurable nanoparticle architectures on a gold surface over large areas. Specifically, the assembly of individual colloidal plasmonic nanoparticles with different shapes and sizes is controlled by oligonucleotides containing “locked” nucleic acids and confined environments provided by polymer pores to yield oriented architectures that feature tunable arrangements and independently controllable distances at both nanometer and micrometer length scales. These structures, which would be difficult to construct via other common assembly methods, provide a platform to systematically study and control light-matter interactions in nanoparticle-based optical materials. The generality and potential of this approach are explored by identifying a broadband absorber with a solvent polarity response that allows dynamic tuning of visible light absorption.
A pathway for mitotic chromosome formation Science (IF 37.205) Pub Date : 2018-01-18 Johan H. Gibcus, Kumiko Samejima, Anton Goloborodko, Itaru Samejima, Natalia Naumova, Johannes Nuebler, Masato T. Kanemaki, Linfeng Xie, James R. Paulson, William C. Earnshaw, Leonid A. Mirny, Job Dekker
Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C of synchronous DT40 cell cultures with polymer simulations. We show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner and arrays of consecutive 60 kb loops are formed. During prometaphase ~80 kb inner loops are nested within ~400 kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral-staircase condensin scaffold. The size of helical turns progressively increases during prometaphase to ~12 Mb. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins while condensin II is required for helical winding.
Atomic-resolution transmission electron microscopy of electron beam–sensitive crystalline materials Science (IF 37.205) Pub Date : 2018-01-18 Daliang Zhang, Yihan Zhu, Lingmei Liu, Xiangrong Ying, Chia-En Hsiung, Rachid Sougrat, Kun Li, Yu Han
High-resolution imaging of electron beam-sensitive materials is one of the most difficult applications of transmission electron microscopy (TEM). The challenges are manifold, including the acquisition of images with extremely low beam doses, the time-constrained search for crystal zone axes, the precise image alignment, and the accurate determination of the defocus value. We develop a suite of methods to fulfill these requirements and acquire atomic-resolution TEM images of several metal organic frameworks that are generally recognized as highly sensitive to electron beams. The high image resolution allows us to identify individual metal atomic columns, various types of surface termination, and benzene rings in the organic linkers. We also apply our methods to other electron beam–sensitive materials, including the organic-inorganic hybrid perovskite CH3NH3PbBr3.
Frankenstein lives on Science (IF 37.205) Pub Date : 2018-01-12 Henk van den Belt
It was 200 years ago that Mary Shelley's Frankenstein; or, The Modern Prometheus was published. Over the decades, this gothic tale has captured the popular imagination through the numerous theater productions and films it inspired. The story is commonly taken to imply a dire warning about the dangers of scientific hubris. Just mention the name Frankenstein and laypersons think of scientists “playing God.” In the common view, the inevitable consequence of Frankenstein's alleged transgression—bestowing life on inanimate matter—was that he created a monster that would wreak havoc on his family and friends. Frankenstein's name is repeatedly invoked in debates about emerging technologies like biotech, nanotech, synthetic biology, and artificial intelligence. However, the view of Shelley's story as a cautionary tale about scientific hubris, although dominant, is only one possible interpretation. Her novel, actually, is a multilayered story full of ambivalences and much subtler than most Hollywood versions. It naturally lends itself to diverse interpretations.
News at a glance Science (IF 37.205) Pub Date : 2018-01-12 American Association for the Advancement of Science
In science news around the world, the U.S. National Football League provides $16 million for medical research on concussions and other football-related illnesses, and the World Health Organization approves a new, long-lasting vaccine for typhoid fever. China announces it will build a new research and development park in Beijing to develop artificial intelligence technologies, and South Korean universities refuse to renew their contracts with Elsevier for access to its ScienceDirect database because of a price hike. Scientists install new devices at the South Pole to measure neutrinos, and a volunteer discovers the largest prime number, containing more than 23 million digits. And the U.S. Department of the Interior decides to review certain grants to universities and nonprofit groups to ensure they align with the priorities of President Donald Trump's administration.
DOE pushes for useful quantum computing Science (IF 37.205) Pub Date : 2018-01-12 Adrian Cho
The U.S. Department of Energy (DOE) is joining the quest to develop quantum computers, devices that would exploit quantum mechanics to crack problems that overwhelm conventional computers. The initiative comes as Google and other companies race to build a quantum computer that can demonstrate "quantum supremacy" by beating classical computers on a test problem. But reaching that milestone will not mean practical uses are at hand, and the new $40 million DOE effort is intended to spur the development of useful quantum computing algorithms for its work in chemistry, materials science, nuclear physics, and particle physics. With the resources at its 17 national laboratories, DOE could play a key role in developing the machines, researchers say, although finding problems with which quantum computers can help isn't so easy.
In Pakistan, surveillance for polio reveals a paradox Science (IF 37.205) Pub Date : 2018-01-12 Leslie Roberts
Last year polio fighters could smell victory in Pakistan, which many believe will be the last country on Earth to harbor the virus. Cases dropped to an all-time low. Blood tests showed that immunity to the poliovirus had never been higher. Surely, there were not enough susceptible children to sustain transmission, and the virus would burn itself out within a year. Unsettling new findings, however, show it is far from gone. In the most extensive effort in any country to scour the environment for traces of the virus, polio workers are finding it widely across Pakistan, in places they thought it had disappeared. They are wondering "just what the hell is going on" and how worried they should be, says epidemiologist Chris Maher of the World Health Organization in Geneva, Switzerland, who runs polio operations in the eastern Mediterranean region. Does this mean the virus is more entrenched than anyone realized and is poised to resurge? Or is this how a virus behaves in its final days—persisting in the environment but not causing disease until it fades out?
Earth scientists list top priorities for space missions Science (IF 37.205) Pub Date : 2018-01-12 Paul Voosen
Earth scientists hope a new priority setting effort will help them make the most of NASA's limited budget for satellite missions that watch over the planet. The so-called decadal survey, issued in January by the National Academies of Sciences, Engineering, and Medicine, laid out the community's consensus wish list, ranging from cloud monitoring to multiwavelength imaging—and recommends a strong dose of competition to keep costs down. The report prioritizes five observations for launch, including hyperspectral imaging, clouds, atmospheric particles, and missions to chart gravity variations and tiny crustal movements. It also advocates creating a new line of $350 million missions targeting seven observations, with competitions to choose three for flight in the next 10 years.
Cuba's 100-year plan for climate change Science (IF 37.205) Pub Date : 2018-01-12 Richard Stone
On its deadly run through the Caribbean last September, Hurricane Irma lashed northern Cuba, inundating coastal settlements and scouring away vegetation. Irma lent new urgency to a Cuban national plan, called Tarea Vida, or Project Life, that bans construction of new homes in threatened coastal areas, mandates relocating people from communities doomed by rising sea levels, calls for an overhaul of the country's agricultural system to shift crop production away from saltwater-contaminated areas, and spells out the need to shore up coastal defenses, including by restoring degraded habitat. Project Life stands out for taking a long view: It intends to prepare Cuba for climatological impacts over the next century. Much of the initial funding could come from a $100 million proposal that Cuba plans to submit soon to the Global Climate Fund.
Cliffs of ice spied on Mars Science (IF 37.205) Pub Date : 2018-01-12 Paul Voosen
Scientists have discovered eight cliffs of nearly pure water ice on Mars, some of which stand nearly 100 meters tall. The discovery points to large stores of underground ice buried only a meter or two below the surface at surprisingly low martian latitudes, in regions where ice had not yet been detected. Each cliff seems to be the naked face of a glacier, tantalizing scientists with the promise of a layer-cake record of past martian climates and space enthusiasts with a potential resource for future human bases. Scientists discovered the cliffs with a high-resolution camera on the Mars Reconnaissance Orbiter, revisiting the sites to show their subsequent retreat as a result of vaporization, and their persistence in the martian summer. The hunt should now be on, scientists say, for similar sites closer to the equator.
The long shadow of Frankenstein Science (IF 37.205) Pub Date : 2018-01-12 Kai Kupferschmidt
In January 1818, Mary Shelley published her book Frankenstein, a terrifying story of a doctor who builds a creature from scavenged body parts, then recoils in horror, spurns it, and sees his friends and family destroyed by the monster. Two hundred years later, Frankenstein is still essential reading for anyone working in science. In this special issue, Science examines the lasting legacy of Shelley's book on science and popular culture as well as the potential risks from modern-day, real-life Frankensteins.
How a horror story haunts science Science (IF 37.205) Pub Date : 2018-01-12 Jon Cohen
In conceiving her novel Frankenstein, Mary Shelley was influenced by the nascent medical science of the day and by early experiments on electricity. In return, Frankenstein has haunted science ever since. Shelley's book and subsequent films and plays have become what one author calls "the governing myth of modern biology": a cautionary tale of scientific hubris. The scientific literature, like the popular press, is rife with references to Frankenfood, Frankencells, and Frankendrugs—most of them supposedly monstrous creations. Other papers mentioning Frankenstein analyze the science behind the novel, analyze Shelley's state of mind, or even, in a bizarre twist, draw inspiration from the tale.
Creating a modern monster Science (IF 37.205) Pub Date : 2018-01-12 David Shultz
When Mary Shelley published her story of Victor Frankenstein and his misshapen monster in 1818, she provided little detail about how exactly the doctor built his creation, except that "the dissecting room and the slaughter-house furnished many of [his] materials" and that he infused "a spark of being in the lifeless thing." But what if Shelley had written her book today? Here is an overview of current and future technologies—from lab-grown organs and bionics to gene editing—that she might call on to produce her iconic creature.
Taming the monsters of tomorrow Science (IF 37.205) Pub Date : 2018-01-12 Kai Kupferschmidt
In Mary Shelley's novel, the scientist Victor Frankenstein fears that creating a female companion to his unhappy monster could lead to a "race of devils" that could drive humanity extinct. Today, some scientists worry about scientific advances in the real world that could kill all of humanity, or at least end civilization as we know it. Some two dozen researchers at three academic centers are studying these "existential risks"—including labmade viruses, armies of nanobots, and artificial intelligence—and what can be done about them. But critics say their scenarios are far-fetched and distract from real existential dangers, including climate change and nuclear war.
A glossary of Frankenwords Science (IF 37.205) Pub Date : 2018-01-12 Jon Cohen
Along with fears about scientific overreach, Mary Shelley's novel has inspired hundreds of whimsical names for products and phenomena—from Frankencells and Frankengenes to Frankenslime and Frankenswine. Here's a selection.
Detecting the building blocks of aromatics Science (IF 37.205) Pub Date : 2018-01-12 Christine Joblin, José Cernicharo
Interstellar clouds are sites of active organic chemistry (1). Many small, gasphase molecules are found in the dark parts of the clouds that are protected from ultraviolet (UV) photons, but these molecules photodissociate in the external layers of the cloud that are exposed to stellar radiation (see the photo). These irradiated regions are populated by large polycyclic aromatic hydrocarbons (PAHs) with characteristic infrared (IR) emission features. These large aromatics are expected to form from benzene (C6H6), which is, however, difficult to detect because it does not have a permanent dipole moment and can only be detected via its IR absorption transitions against a strong background source (2). On page 202 of this issue, McGuire et al. (3) report the detection of benzonitrile (c-C6H5CN) with radio telescopes. Benzonitrile likely forms in the reaction of CN with benzene; from its observation, it is therefore possible to estimate the abundance of benzene itself.
Improbable Big Birds Science (IF 37.205) Pub Date : 2018-01-12 Catherine E. Wagner
Darwin's finches, a group of 18 species endemic to the Galápagos archipelago, are a classic example of adaptive radiation—the process whereby a single ancestral species multiplies in number to produce divergent species, often in rapid succession (1). These birds are evolutionary biologists' most celebrated example of natural selection in action. On page 224 of this issue, Lamichhaney et al. (2) have succeeded in observing a process even more elusive than natural selection—the formation of a new species (speciation). Because speciation typically takes place on time scales that are too long for direct human observation, before now it was only in organisms with very fast generation times, such as viruses and bacteria, that scientists had directly observed this process [for example, (3)]. Lamichhaney et al. show through direct observation and DNA sequencing that new species can form very rapidly: within three generations. The key, in this case, is hybridization between different species.
Malaria parasite evolution in a test tube Science (IF 37.205) Pub Date : 2018-01-12 Jane M. Carlton
Malaria is an infectious disease caused by the Plasmodium parasite, and transmitted by Anopheles mosquitoes. In 2016, a staggering 216 million cases of malaria and 445,000 deaths were recorded, mostly in Africa, although half of the world's population in 91 countries is at risk of the disease (1). Malaria prevention methods include control of the mosquito with insecticide-treated bed nets and indoor residual spraying of insecticides. Prompt diagnosis through the use of rapid diagnostic tests is also key. Although there is a malaria vaccine, RTS,S/AS01, it shows limited efficacy and has yet to be used widely. However, the frontline against malaria is antimalarial drugs, in particular artemisinin-based combination therapies (ACTs), which are mixtures of artemisinin and its derivatives from the Chinese sweet wormwood herb, with drugs such as piperaquine. Alarmingly, the parasite is now resistant to most drugs that have been developed (see the figure). It is imperative that we identify new inhibitors if progress in reducing malaria is to be sustained. On page 191 of this issue, Cowell et al. (2) present a major step forward, revealing new antimalarial drug targets and their possible resistance mechanisms.
TRPM channels come into focus Science (IF 37.205) Pub Date : 2018-01-12 Chanhyung Bae, Andres Jara-Oseguera, Kenton J. Swartz
Transient receptor potential (TRP) channels were first identified in photoreceptors of the fruit fly (1, 2). In mammals, six major families of TRP channels play key roles in sensing stimuli such as light, temperature, membrane lipids, and intracellular Ca2+. In 2013, two landmark publications revealed the cryo–electron microscopy (cryo-EM) structure of the heat- and capsaicin-activated TRPV1 channel (3, 4). Two articles in this issue report cryo-EM structures of cation-selective TRPM channels. On page 228, Autzen et al. (5) describe TRPM4, which is activated by intracellular Ca2+ and involved in controlling arterial tone, cardiac rhythm, and the immune response (6). On page 237, Yin et al. (7) report on TRPM8, which senses cold and menthol and may serve as a cancer biomarker (8).
Coherent excitations revealed and calculated Science (IF 37.205) Pub Date : 2018-01-12 Antoine Georges
Quantum entities manifest themselves as either particles or waves. In a physical system containing a very large number of identical particles, such as electrons in a material, individualistic (particle-like) behavior prevails at high temperatures. At low temperatures, collective behavior emerges, and excitations of the system in this regime are best described as waves—long-lived phenomena that are periodic in both space and time and often dubbed “coherent excitations” by physicists. On page 186 of this issue, Goremychkin et al. (1) used experiment and theory to describe the emergence of coherent excitations in a complex quantum system with strong interactions. They studied a cerium-palladium compound, CePd3, in which the very localized electrons of 4f orbitals of Ce interact with the much more itinerant conduction electrons of the extended d orbitals of Pd at low temperatures to create a wavelike state.
Silencing stemness in T cell differentiation Science (IF 37.205) Pub Date : 2018-01-12 Amanda N. Henning, Christopher A. Klebanoff, Nicholas P. Restifo
Functional diversity in multicellular organisms is achieved through the differentiation of stem cells. During this process, stem cells must retain both the capacity for self-renewal and the ability to differentiate into highly specialized cell types to produce a diverse array of tissues, each with distinct functions and organization. This plasticity is achieved through alterations to the epigenome, heritable and reversible modifications to DNA and histones that affect chromatin structure and gene transcription without altering the DNA sequence itself. Alterations to the epigenome enable cell type–specific transcriptional control that can change dynamically over the life of a cell. Such flexibility and responsiveness are instrumental in directing gene expression changes throughout cellular differentiation and lineage specification. The acquisition of more specialized functions during differentiation requires not only that the epigenome turn “on” genes involved in lineage commitment, it also necessitates that genes associated with stemness are simultaneously turned “off” (1). On page 177 of this issue, Pace et al. (2) demonstrate that this phenomenon exists in CD8+ T cells, in which epigenetic repression of stemness-associated genes by the histone methyltransferase SUV39H1 is required for T cell effector differentiation. Understanding these mechanisms addresses important questions in immunology and is applicable to cancer immunotherapy.
Global science for city policy Science (IF 37.205) Pub Date : 2018-01-12 Michele Acuto
Research and data are increasingly at the heart of how we conceive of urban governance. Urban control rooms and city dashboards championed by cities like Chicago, São Paulo, and London have been promising real-time snapshots and tracking over time of urban systems, via geolocated mobility data sets, social media inputs, environmental sensors, and other tools (1). At the international level, the importance of urban research and data has been enshrined in major United Nations (UN) processes, from the UN New Urban Agenda, the Sendai Framework for Disaster Risk Reduction, and the Sustainable Development Goals (SDGs) to the World Data Forum (2). Yet overall, the global state of data-informed urban governance remains underdeveloped, often promising, as with the dashboards, more than it actually delivers. It is time for a step change. A truly global reform of scientific advice to cities must take place on multiple interconnected fronts, linking a UN action plan on science and the future of cities, a “good advice” commitment by the private sector, and formalized partnerships for urban science at the local level. This scientifically informed urban reform, ripe for discussion at the upcoming UN World Urban Forum in February, can be uniquely bold in recognizing the potential of municipal action on global challenges. Despite being considered the “lowest” level of governance, cities have developed a track record of global action on key matters like climate, disasters, and health, often surpassing, in speed, commitments, and global coverage, that of nations.
Revisit a cautionary classic Science (IF 37.205) Pub Date : 2018-01-12 Dov Greenbaum
The tale of Victor Frankenstein and his monstrous creation has become a universal touchstone that encapsulates our visceral fears regarding the promises, perils, and pitfalls of countless diverse areas of science and technology. A new annotated volume of Mary Shelley's original work is an effort to reintroduce the story to new generations of researchers who, like many before them, ought to take its lessons to heart.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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