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.
Our idiosyncracies Science (IF 37.205) Pub Date : 2018-01-12 Michael A. Goldman
Joining the ranks of a burgeoning number of professional scientists turned professional writers, Liam Drew, a practicing neuroscientist for 12 years, has put down his microfuge tubes and taken up the charge of communicating with the public about science. His first book, I, Mammal: The Story of What Makes Us Mammals, stands out as a clear, conversational (sometimes to a fault), and engaging work that is especially good at explaining how evolutionary biology works.
The epigenetic control of stemness in CD8+ T cell fate commitment Science (IF 37.205) Pub Date : 2018-01-12 Luigia Pace, Christel Goudot, Elina Zueva, Paul Gueguen, Nina Burgdorf, Joshua J. Waterfall, Jean-Pierre Quivy, Geneviève Almouzni, Sebastian Amigorena
After priming, naïve CD8+ T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8+ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell–related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in Suv39h1-defective T cell effectors. As a result, Suv39h1-defective CD8+ T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8+ T effector terminal differentiation.
Coherent band excitations in CePd3: A comparison of neutron scattering and ab initio theory Science (IF 37.205) Pub Date : 2018-01-12 Eugene A. Goremychkin, Hyowon Park, Raymond Osborn, Stephan Rosenkranz, John-Paul Castellan, Victor R. Fanelli, Andrew D. Christianson, Matthew B. Stone, Eric D. Bauer, Kenneth J. McClellan, Darrin D. Byler, Jon M. Lawrence
In common with many strongly correlated electron systems, intermediate valence compounds are believed to display a crossover from a high-temperature regime of incoherently fluctuating local moments to a low-temperature regime of coherent hybridized bands. We show that inelastic neutron scattering measurements of the dynamic magnetic susceptibility of CePd3 provides a benchmark for ab initio calculations based on dynamical mean field theory. The magnetic response is strongly momentum dependent thanks to the formation of coherent f-electron bands at low temperature, with an amplitude that is strongly enhanced by local particle-hole interactions. The agreement between experiment and theory shows that we have a robust first-principles understanding of the temperature dependence of f-electron coherence.
Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics Science (IF 37.205) Pub Date : 2018-01-12 Annie N. Cowell, Eva S. Istvan, Amanda K. Lukens, Maria G. Gomez-Lorenzo, Manu Vanaerschot, Tomoyo Sakata-Kato, Erika L. Flannery, Pamela Magistrado, Edward Owen, Matthew Abraham, Gregory LaMonte, Heather J. Painter, Roy M. Williams, Virginia Franco, Maria Linares, Ignacio Arriaga, Selina Bopp, Victoria C. Corey, Nina F. Gnädig, Olivia Coburn-Flynn, Christin Reimer, Purva Gupta, James M. Murithi, Pedro A. Moura, Olivia Fuchs, Erika Sasaki, Sang W. Kim, Christine H. Teng, Lawrence T. Wang, Aslı Akidil, Sophie Adjalley, Paul A. Willis, Dionicio Siegel, Olga Tanaseichuk, Yang Zhong, Yingyao Zhou, Manuel Llinás, Sabine Ottilie, Francisco-Javier Gamo, Marcus C. S. Lee, Daniel E. Goldberg, David A. Fidock, Dyann F. Wirth, Elizabeth A. Winzeler
Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target–inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.
Exposed subsurface ice sheets in the Martian mid-latitudes Science (IF 37.205) Pub Date : 2018-01-12 Colin M. Dundas, Ali M. Bramson, Lujendra Ojha, James J. Wray, Michael T. Mellon, Shane Byrne, Alfred S. McEwen, Nathaniel E. Putzig, Donna Viola, Sarah Sutton, Erin Clark, John W. Holt
Thick deposits cover broad regions of the Martian mid-latitudes with a smooth mantle; erosion in these regions creates scarps that expose the internal structure of the mantle. We investigated eight of these locations and found that they expose deposits of water ice that can be >100 meters thick, extending downward from depths as shallow as 1 to 2 meters below the surface. The scarps are actively retreating because of sublimation of the exposed water ice. The ice deposits likely originated as snowfall during Mars’ high-obliquity periods and have now compacted into massive, fractured, and layered ice. We expect the vertical structure of Martian ice-rich deposits to preserve a record of ice deposition and past climate.
Detection of the aromatic molecule benzonitrile (c-C6H5CN) in the interstellar medium Science (IF 37.205) Pub Date : 2018-01-12 Brett A. McGuire, Andrew M. Burkhardt, Sergei Kalenskii, Christopher N. Shingledecker, Anthony J. Remijan, Eric Herbst, Michael C. McCarthy
Polycyclic aromatic hydrocarbons and polycyclic aromatic nitrogen heterocycles are thought to be widespread throughout the universe, because these classes of molecules are probably responsible for the unidentified infrared bands, a set of emission features seen in numerous Galactic and extragalactic sources. Despite their expected ubiquity, astronomical identification of specific aromatic molecules has proven elusive. We present the discovery of benzonitrile (c-C6H5CN), one of the simplest nitrogen-bearing aromatic molecules, in the interstellar medium. We observed hyperfine-resolved transitions of benzonitrile in emission from the molecular cloud TMC-1. Simple aromatic molecules such as benzonitrile may be precursors for polycyclic aromatic hydrocarbon formation, providing a chemical link to the carriers of the unidentified infrared bands.
Ordered macro-microporous metal-organic framework single crystals Science (IF 37.205) Pub Date : 2018-01-12 Kui Shen, Lei Zhang, Xiaodong Chen, Lingmei Liu, Daliang Zhang, Yu Han, Junying Chen, Jilan Long, Rafael Luque, Yingwei Li, Banglin Chen
We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional–ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent–induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.
Antagonism toward the intestinal microbiota and its effect on Vibrio cholerae virulence Science (IF 37.205) Pub Date : 2018-01-12 Wenjing Zhao, Florence Caro, William Robins, John J. Mekalanos
The bacterial type VI secretion system (T6SS) is a nanomachine that delivers toxic effector proteins into target cells, killing them. In mice, we found that the Vibrio cholerae T6SS attacks members of the host commensal microbiota in vivo, facilitating the pathogen’s colonization of the gut. This microbial antagonistic interaction drives measurable changes in the pathogenicity of V. cholerae through enhanced intestinal colonization, expression of bacterial virulence genes, and activation of host innate immune genes. Because ablation of mouse commensals by this enteric pathogen correlated with more severe diarrheal symptoms, we conclude that antagonism toward the gut microbiota could improve the fitness of V. cholerae as a pathogen by elevating its transmission to new susceptible hosts.
Spatial representations of self and other in the hippocampus Science (IF 37.205) Pub Date : 2018-01-12 Teruko Danjo, Taro Toyoizumi, Shigeyoshi Fujisawa
An animal’s awareness of its location in space depends on the activity of place cells in the hippocampus. How the brain encodes the spatial position of others has not yet been identified. We investigated neuronal representations of other animals’ locations in the dorsal CA1 region of the hippocampus with an observational T-maze task in which one rat was required to observe another rat’s trajectory to successfully retrieve a reward. Information reflecting the spatial location of both the self and the other was jointly and discretely encoded by CA1 pyramidal cells in the observer rat. A subset of CA1 pyramidal cells exhibited spatial receptive fields that were identical for the self and the other. These findings demonstrate that hippocampal spatial representations include dimensions for both self and nonself.
Social place-cells in the bat hippocampus Science (IF 37.205) Pub Date : 2018-01-12 David B. Omer, Shir R. Maimon, Liora Las, Nachum Ulanovsky
Social animals have to know the spatial positions of conspecifics. However, it is unknown how the position of others is represented in the brain. We designed a spatial observational-learning task, in which an observer bat mimicked a demonstrator bat while we recorded hippocampal dorsal-CA1 neurons from the observer bat. A neuronal subpopulation represented the position of the other bat, in allocentric coordinates. About half of these “social place-cells” represented also the observer’s own position—that is, were place cells. The representation of the demonstrator bat did not reflect self-movement or trajectory planning by the observer. Some neurons represented also the position of inanimate moving objects; however, their representation differed from the representation of the demonstrator bat. This suggests a role for hippocampal CA1 neurons in social-spatial cognition.
Rapid hybrid speciation in Darwin’s finches Science (IF 37.205) Pub Date : 2018-01-12 Sangeet Lamichhaney, Fan Han, Matthew T. Webster, Leif Andersson, B. Rosemary Grant, Peter R. Grant
Homoploid hybrid speciation in animals has been inferred frequently from patterns of variation, but few examples have withstood critical scrutiny. Here we report a directly documented example, from its origin to reproductive isolation. An immigrant Darwin’s finch to Daphne Major in the Galápagos archipelago initiated a new genetic lineage by breeding with a resident finch (Geospiza fortis). Genome sequencing of the immigrant identified it as a G. conirostris male that originated on Española >100 kilometers from Daphne Major. From the second generation onward, the lineage bred endogamously and, despite intense inbreeding, was ecologically successful and showed transgressive segregation of bill morphology. This example shows that reproductive isolation, which typically develops over hundreds of generations, can be established in only three.
Structure of the human TRPM4 ion channel in a lipid nanodisc Science (IF 37.205) Pub Date : 2018-01-12 Henriette E. Autzen, Alexander G. Myasnikov, Melody G. Campbell, Daniel Asarnow, David Julius, Yifan Cheng
Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage-dependent manner but, unlike many other TRP channels, is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3-angstrom resolution, as determined by single-particle cryo–electron microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium-binding site within the intracellular side of the S1-S4 domain. The structures correspond to two distinct closed states. Calcium binding induces conformational changes that likely prime the channel for voltage-dependent opening.
CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi Science (IF 37.205) Pub Date : 2018-01-12 Irina Leonardi, Xin Li, Alexa Semon, Dalin Li, Itai Doron, Gregory Putzel, Agnieszka Bar, Daniel Prieto, Maria Rescigno, Dermot P. B. McGovern, Jesus Pla, Iliyan D. Iliev
Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn’s disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.
Structure of the cold- and menthol-sensing ion channel TRPM8 Science (IF 37.205) Pub Date : 2018-01-12 Ying Yin, Mengyu Wu, Lejla Zubcevic, William F. Borschel, Gabriel C. Lander, Seok-Yong Lee
Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo–electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer. The structure suggests that the menthol-binding site is located within the voltage-sensor–like domain and thus provides a structural glimpse of the design principle of the molecular transducer for cold and menthol sensation.
Gene therapy comes of age Science (IF 37.205) Pub Date : 2018-01-12 Cynthia E. Dunbar, Katherine A. High, J. Keith Joung, Donald B. Kohn, Keiya Ozawa, Michel Sadelain
After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells. We also discuss emerging genome editing technologies that should further advance the scope and efficacy of gene therapy approaches.
Fatty acyl recognition and transfer by an integral membrane S-acyltransferase Science (IF 37.205) Pub Date : 2018-01-12 Mitra S. Rana, Pramod Kumar, Chul-Jin Lee, Raffaello Verardi, Kanagalaghatta R. Rajashankar, Anirban Banerjee
DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl–coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation. The acyl chain binds in a cavity formed by the transmembrane domain. We propose a mechanism for acyl chain–length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains.
Ideal Weyl points and helicoid surface states in artificial photonic crystal structures Science (IF 37.205) Pub Date : 2018-01-11 Biao Yang, Qinghua Guo, Ben Tremain, Rongjuan Liu, Lauren E. Barr, Qinghui Yan, Wenlong Gao, Hongchao Liu, Yuanjiang Xiang, Jing Chen, Chen Fang, Alastair Hibbins, Ling Lu, Shuang Zhang
Weyl points are the crossings of linearly dispersing energy bands of three-dimensional crystals, providing the opportunity to explore a variety of intriguing phenomena such as topologically protected surface states and chiral anomalies. However, the lack of an ideal Weyl system in which the Weyl points all exist at the same energy and are separated from any other bands, poses a serious limitation to the further development of Weyl physics and potential applications. By experimentally characterizing a microwave photonic crystal of saddle-shaped metallic coils, we observe ideal Weyl points that are related to each other through symmetry operations. Topological surface states exhibiting helicoidal structure have also been demonstrated. Our system provides a photonic platform for exploring ideal Weyl systems and developing possible topological devices.
Observation of bulk Fermi arc and polarization half charge from paired exceptional points Science (IF 37.205) Pub Date : 2018-01-11 Hengyun Zhou, Chao Peng, Yoseob Yoon, Chia Wei Hsu, Keith A. Nelson, Liang Fu, John D. Joannopoulos, Marin Soljačić, Bo Zhen
The ideas of topology have found tremendous success in closed physical systems, but even richer properties exist in the more general open or dissipative framework. We theoretically propose and experimentally demonstrate a bulk Fermi arc that develops from non-Hermitian radiative losses in an open system of photonic crystal slabs. Moreover, we discover half-integer topological charges in the polarization of far-field radiation around the bulk Fermi arc. Both phenomena are shown to be direct consequences of the non-Hermitian topological properties of exceptional points, where resonances coincide in their frequencies and linewidths. Our work connects the fields of topological photonics, non-Hermitian physics and singular optics, providing a framework to explore more complex non-Hermitian topological systems.
Progress on reproducibility Science (IF 37.205) Pub Date : 2018-01-05 Jeremy Berg
Ideas supported by well-defined and clearly described methods and evidence are one of the cornerstones of science. After several publications indicated that a substantial number of scientific reports may not be readily reproducible, the scientific community and public began engaging in discussions about mechanisms to measure and enhance the reproducibility of scientific projects. In this context, several innovative steps have been taken in recent years. The results of these efforts confirm that improving reproducibility will require persistent and adaptive responses, and as we gain experience, implementation of the best possible practices.
What's coming up in 2018 Science (IF 37.205) Pub Date : 2018-01-05 American Association for the Advancement of Science
Science's news staff predicts areas of research and policy likely to be in the news this year. Among them: Astronomers may generate a dazzling image of the supermassive black hole at the heart of our galaxy, and new sources of ancient DNA should amplify the power of this molecular relic to shed light on the origins and diversity of human ancestors. A European court is expected to rule on whether gene-edited crops are subject to regulations on organisms modified using other genetic engineering techniques. In clinical research, scientists will test whether injectable, long-lasting antiretroviral drugs work as well as pills taken daily to treat HIV. And many scientists, energized by their opposition to the science and environmental policies of U.S. President Donald Trump and Republican-controlled Congress, are running for office.
Watching the teen brain grow Science (IF 37.205) Pub Date : 2018-01-05 Meredith Wadman
Adolescence is a time of extraordinarily important brain changes. And thanks to an unprecedented study now being launched, scientists will be able to examine those changes in depth, using MRI to define what normal growth looks like—and helping clarify what can go awry in teenage brains. The Adolescent Brain Cognitive Development Study—or ABCD Study—is a $300 million effort funded by the National Institutes of Health that will scan the brains of some 10,000 U.S. youths, beginning when they are 9 and 10 years old and imaging them every 2 years for 10 years. In addition to collecting scans of brain structure and function, the research teams at 21 study sites around the country will regularly gather a trove of other information from each youngster, from psychological, cognitive, and environmental data to biological specimens such as DNA. The hope is that by enrolling children young, before influences like substance use and sports injuries kick in, scientists will be able to untangle chicken-and-egg questions that correlational studies can't—questions about everything from mental illness to the impact of marijuana on the developing brain. The response so far has been encouraging: Two-thirds of the way through a 2-year enrollment period that ends in September, the researchers have signed up more than 6800 children. And anonymized data from the first 4500 of them are due to be deposited in a publicly accessible database later this month.
Americas peopled in a single wave, ancient genome reveals Science (IF 37.205) Pub Date : 2018-01-05 Michael Price
A rare smidgen of ancient DNA has sharpened the picture of one of humanity's greatest migrations. Some 15,000 to 25,000 years ago, people wandered from Asia to North America across a now-submerged land called Beringia, which once connected Siberia and Alaska. But exactly when these ancient settlers crossed and how many migrations occurred are hotly debated. Now, researchers have sequenced the oldest full genome from an ancient American, an 11,500-year-old infant from the site of Upward Sun River in central Alaska. The child's genome suggests that some settlers stayed in Beringia while another group headed south and formed the population from which all living Native Americans descend. That supports the idea that Asian migrants lingered in Beringia and became genetically isolated, the so-called Beringian standstill model.
Cancer institute head touts big data and basic research Science (IF 37.205) Pub Date : 2018-01-05 Jocelyn Kaiser
Cancer researchers had worried that President Donald Trump might choose an unconventional candidate to replace Harold Varmus as director of the National Cancer Institute in Bethesda, Maryland. But his choice, announced in June 2017, allayed their fears. Norman "Ned" Sharpless, who was then director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill, checked all the right boxes for the community: He is a physician-scientist who treats patients, he has started two biotech companies, and he runs a basic research lab. In an interview last month, Sharpless declined to lay out specific plans for the $5.7 billion institute. But he stressed three areas: big data, basic research, and translating discoveries into devices and treatments.
Mars methane rises and falls with the seasons Science (IF 37.205) Pub Date : 2018-01-05 Eric Hand
On Earth, atmospheric methane is a prominent sign of life. On Mars, the story is more complicated. Trace detections of methane, alongside glimpses of larger spikes, have fueled debates about biological and nonbiological sources of the gas. Now, NASA scientists have announced a new twist in the tale: Methane regularly rises to a peak in late northern summer in a seasonal pattern. The swings are larger than can be explained by the planet's seasonal freeze-thaw cycles. The wiggles are a mystery within a larger mystery: claims of methane spikes an order of magnitude or two higher than the background. Some scientists say meteor showers could be responsible, by depositing carbonaceous material in the atmosphere that reacts to form methane. A close encounter on 24 January with debris from a comet could provide a chance to test the hypothesis.
Germany steps up to the plate in global health Science (IF 37.205) Pub Date : 2018-01-05 Kai Kupferschmidt
Germany has long shied away from playing any major role on the global stage, and especially in public health, orVolksgesundheit, a label used to justify Nazi crimes in the past. But now, Germany's role in global health is growing rapidly. The German government has embarked on several international health initiatives and has doubled its financial contributions to global health aid. The Bill & Melinda Gates Foundation plans to set up a Berlin office next year; the German capital will also host a new, international center focused on the rising threat of antimicrobial resistance. Germany's own research output in global health is still lagging, however.
Earth-based planet finders power up Science (IF 37.205) Pub Date : 2018-01-05 Daniel Clery
NASA's Kepler spacecraft has racked up thousands of exoplanet discoveries since its launch in 2009, but before Kepler, the workhorses of exoplanet identification were ground-based instruments that measure tiny stellar wobbles caused by the gravity of an orbiting planet. They are now undergoing a quiet renaissance. The new generation of these devices may be precise enough to find a true Earth twin: a planet with the same mass as ours, orbiting a sunlike star once a year. That's something Kepler—sensitive to planet size, but not mass—can't do. Over the past few months, two new third-generation instruments have opened their eyes to the sky and nearly two dozen others are either under construction or have recently begun service.
Chemical martyrs Science (IF 37.205) Pub Date : 2018-01-05 Richard Stone
During the Iran-Iraq War of the 1980s, Iraq on scores of occasions shelled Iranian soldiers and villagers with sulfur mustard. And for the first time ever on a battlefield, nerve agents including sarin and tabun were unleashed by Iraqi forces. All told, the chemical onslaught killed nearly 5000 Iranians and sickened more than 100,000. Three decades later, about 56,000 Iranians are coping with lingering health effects from mustard, ranging from skin lesions and failing corneas to chronic obstructive lung disease and possibly cancer. The scale of the atrocities means that Iran has a unique opportunity to study the long-term effects of chemical weapons. A dozen research centers across the nation are seeking to uncover how wartime mustard exposures wreaked molecular mayhem that, decades later, triggers illnesses and death. They also may soon begin probing for long-term health effects of nerve agents.
How to defeat a nerve agent Science (IF 37.205) Pub Date : 2018-01-05 Richard Stone
The long-term effects of nerve agents remain uncertain, but with the right antidotes, these poisons need not be an immediate death sentence. U.S. soldiers in 1991's Gulf War carried autoinjectors filled with drugs that—in principle—would keep them breathing and protect them from seizures if Iraqi forces again unleashed nerve agents. They never did, most historians agree, but the threat remains real today, as chemical attacks in Syria's ongoing civil war make clear. The likeliest nerve agent to be used in future attacks, defense experts say, is sarin: It's as volatile as water and disperses widely in the air. The threat of future nerve agent attacks is spurring urgent efforts to find better countermeasures, with several promising compounds in the pipeline.
Weapons in waiting Science (IF 37.205) Pub Date : 2018-01-05 Richard Stone
On the night of 26 October 2002, Russian special forces raided the Dubrovka Theater in Moscow, where terrorists were holding several hundred hostages. They had pumped a narcotic aerosol into the hall, aiming to incapacitate the terrorists. But the vapor—composed of two fentanyl derivatives—was so potent that many hostages lapsed into a coma, and 124 of them died. The botched raid marked the debut of a new chemical weapon, one of many that worry experts. The U.S. Department of Homeland Security has a list of about 100 chemicals that pose a serious risk of being weaponized, and these have been categorized according to their toxidrome, or the broad set of symptoms they trigger. The potential threats are spurring a search for new countermeasures.
The genomics of climate change Science (IF 37.205) Pub Date : 2018-01-05 Mark J. Fitzpatrick, Allan H. Edelsparre
Human-induced climate change is causing rapidly changing global temperatures and extreme fluctuations in precipitation. These changes force organisms to adapt and evolve or face extinction. Understanding and predicting the evolutionary responses to climate change is critical for preserving biodiversity, but predictions are challenging because they involve interactions between adaptive plasticity (such as altered breeding times) and evolved responses (such as increased metabolism). On page 83 of this issue, Bayet al.(1) combine high-resolution genomic sequencing with population trends and global climate predictions to estimate the adaptive potential (that is, the genetic variation necessary for adaptation) of yellow warblers (see the photo) to climate change and predict future population declines. In doing so, they produce a powerful tool for estimating genomic vulnerability to climate change and locate candidate genes that are key for climate change adaptation.
A new mitotic activity comes into focus Science (IF 37.205) Pub Date : 2018-01-05 Joshua C. Saldivar, Karlene A. Cimprich
During mitosis, each duplicated chromosome must be accurately attached to the microtubule spindle, which pulls the chromosomes to opposite poles of the cell, where they are segregated to daughter cells. A number of mitotic kinases orchestrate mitosis to ensure accurate segregation, including cyclin-dependent kinase 1 (CDK1), the Polo-like kinases, and the Aurora kinases (1). The kinase ATR (ataxia telangiectasia and Rad3-related), which is involved in DNA damage responses during interphase of the cell cycle, has also been shown to prevent chromosome segregation errors (2). However, this role of ATR was presumed to be an indirect effect. On page 108 of this issue, Kabecheet al.(3) unveil a mitosis-specific ATR activity that ensures proper chromosome segregation and that this activity is dependent on a specific three-stranded nucleic acid structure known as an R loop.
Precision medicine using microbiota Science (IF 37.205) Pub Date : 2018-01-05 Christian Jobin
Accumulating evidence indicates that dysregulation of microbiota-host interactions associates with various diseases, including inflammatory bowel diseases (IBDs), colorectal cancer, diabetes, and liver cirrhosis (1). Recently, research has generated paradigm shifts in concepts about the interactions between bacteria and cancer therapeutic drugs. For example, bacteria modulate the antitumor efficacy in preclinical models of various chemotherapies (2–4) and immunotherapeutic agents (5,6). Conceptually, these findings suggest that bacteria-mediated interactions with the immune system are essential for optimal drug efficacy. However, there is limited information regarding the functional impact of the composition of the human microbiome and therapeutic outcomes in cancer patients. On pages 91, 97, and 104 of this issue, Routyet al.(7), Gopalakrishnanet al.(8), and Matsonet al.(9), respectively, address this important issue and demonstrate that patients can be stratified into responders and nonresponders to immunotherapy on the basis of the composition of their intestinal microbiomes, suggesting that microbiota should be considered when assessing therapeutic intervention.
Mind the seafloor Science (IF 37.205) Pub Date : 2018-01-05 Antje Boetius, Matthias Haeckel
As human use of rare metals has diversified and risen with global development, metal ore deposits from the deep ocean floor are increasingly seen as an attractive future resource. Japan recently completed the first successful test for zinc extraction from the deep seabed, and the number of seafloor exploration licenses filed at the International Seabed Authority (ISA) has tripled in the past 5 years. Seafloor-mining equipment is being tested, and industrial-scale production in national waters could start in a few years. We call for integrated scientific studies of global metal resources, the fluxes and fates of metal uses, and the ecological footprints of mining on land and in the sea, to critically assess the risks of deep-sea mining and the chances for alternative technologies. Given the increasing scientific evidence for long-lasting impacts of mining on the abyssal environment, precautionary regulations for commercial deep-sea mining are essential to protect marine ecosystems and their biodiversity.
Lung inflammation originating in the gut Science (IF 37.205) Pub Date : 2018-01-05 Jenny Mjösberg, Anna Rao
Innate lymphoid cells (ILCs) are a type of immune cell that are considered to be tissue-resident gatekeepers situated in mucosal membranes, where they contribute to both homeostasis and pathology (1). In healthy individuals, ILCs are involved in tissue repair, but ILCs have also been shown to participate in several types of inflammation, including allergy and asthma. Whereas ILCs can be found at low frequencies in the blood circulation, mucosal barriers such as the intestine and airways are enriched for ILCs (1). However, whether ILCs are in fact tissue resident in the sense that they self-renew without substantial replenishment from other organs has been a topic of debate. The mechanisms of ILC circulation are important for understanding various types of inflammatory conditions and how they can be treated. On page 114 of this issue, Huanget al.(2) demonstrate that ILC2s are not obligate tissue-resident cells because they can be recruited from the gut to the lung and other organs in response to inflammatory signaling.
The contact sport of rough surfaces Science (IF 37.205) Pub Date : 2018-01-05 Robert W. Carpick
Describing the way two surfaces touch and make contact may seem simple, but it is not. Fully describing the elastic deformation of ideally smooth contacting bodies, under even low applied pressure, involves second-order partial differential equations and fourth-rank elastic constant tensors. For more realistic rough surfaces, the problem becomes a multiscale exercise in surface-height statistics, even before including complex phenomena such as adhesion, plasticity, and fracture. A recent research competition, the “Contact Mechanics Challenge” (1), was designed to test various approximate methods for solving this problem. A hypothetical rough surface was generated, and the community was invited to model contact with this surface with competing theories for the calculation of properties, including contact area and pressure. A supercomputer-generated numerical solution was kept secret until competition entries were received. The comparison of results (2) provides insights into the relative merits of competing models and even experimental approaches to the problem.
Air pollution's hidden impacts Science (IF 37.205) Pub Date : 2018-01-05 Joshua Graff Zivin, Matthew Neidell
Nearly every country in the world regulates air pollution. But how much pollution control is enough? Answering that question requires considerable information about the costs as well as the benefits of regulation. Historically, efforts to measure benefits have focused on averting major health insults, such as respiratory or cardiovascular events that result in hospitalizations or death, which typically only afflict the most vulnerable segments of the population. These health episodes are clearly consequential—e.g., the U.S. Clean Air Act Amendments of 1990 avert an estimated 160,000 deaths and 86,000 hospitalizations annually (1)—but may only represent the tip of the proverbial iceberg, compared to the number of cases of respiratory impairment and other health insults that affect many healthy people every day but do not require hospitalizations or even formal health care encounters. The ubiquity of these less lethal impacts, revealed by emerging economic research on labor productivity and human capital accumulation, suggests that even modest impacts at the individual level can add up to considerable, society-wide impacts across the globe.
The art of space-time Science (IF 37.205) Pub Date : 2018-01-05 Edwin Cartlidge
The Museo Nazionale delle Arti del XXI Secolo (MAXXI; National Museum of 21st Century Arts) in Rome has chosen Einstein as the figurehead of its latest exhibition, entitled Gravity.Imaging the Universe After Einstein. Running until 29 April 2018, the exhibition explores "the meeting point of the current understanding of the cosmos and contemporary art and thinking."
Social science, today Science (IF 37.205) Pub Date : 2018-01-05 David Lazer
Generally, social scientists have been poorly equipped to deal with the 21st-century deluge of large-scale complex data. Computer scientists, well equipped to handle the data, are often ignorant of social theory and of foundational research methods in the social sciences. What is needed is an articulation of core principles of designing research that are accessible to multiple disciplines. Into this breach steps Matthew Salganik withBit by Bit.
Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax Science (IF 37.205) Pub Date : 2018-01-05 Jakub Gruszczyk, Usheer Kanjee, Li-Jin Chan, Sébastien Menant, Benoit Malleret, Nicholas T. Y. Lim, Christoph Q. Schmidt, Yee-Foong Mok, Kai-Min Lin, Richard D. Pearson, Gabriel Rangel, Brian J. Smith, Melissa J. Call, Michael P. Weekes, Michael D. W. Griffin, James M. Murphy, Jonathan Abraham, Kanlaya Sriprawat, Maria J. Menezes, Marcelo U. Ferreira, Bruce Russell, Laurent Renia, Manoj T. Duraisingh, Wai-Hong Tham
Plasmodium vivaxshows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor forP. vivaxreticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition. We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion ofP. vivaxbut not to invasion ofP. falciparum. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also blockP. vivaxentry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes duringP. vivaxinvasion.
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