How to explain the AKT phosphorylation of downstream targets in the wake of recent findings [Letters (Online Only)] PNAS (IF 9.661) Pub Date : 2018-06-15 Anil K. Agarwal
AKT (v-Akt oncogene), a Ser/Thr protein kinase, was also identified as protein kinase B (PKB) (reviewed in ref. 1). There are three known isoforms of AKT1-3. All these AKT isoforms are highly conserved and are recruited to the plasma membrane where they bind to PIP3,4,5 via the PH-domain and are phosphorylated. While Lučić et al. (2) studied AKT1, the study is applicable to all of the AKT isoforms. Among the three AKT isoforms, AKT2 is extensively studied due to its critical role in insulin signaling (3). AKT is a central hub for cellular signal transduction, relaying information …
Reply to Agarwal: Activity against nuclear substrates is not necessarily mediated by nuclear Akt [Letters (Online Only)] PNAS (IF 9.661) Pub Date : 2018-06-15 Thomas A. Leonard
The phosphorylation of Akt substrates in subcellular compartments other than the plasma membrane has previously been proposed to be mediated by the diffusion of activated Akt (1, 2). While this neatly accounts for the observation that Akt is activated by growth factors primarily at the plasma membrane, it poses problems for the cell in controlling the spatial and temporal dynamics of Akt substrate phosphorylation, since Akt would essentially be uncoupled from its activating stimulus. We recently showed that Akt activity is in fact confined to membranes enriched in either PI(3,4,5)P3 or PI(3,4)P2 (3, 4). By restricting Akt activity to the engagement …
Publisher Correction: NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming Nat. Cell. Biol. (IF 20.06) Pub Date : 2018-06-15 Qiang Zhuang, Wenjuan Li, Christina Benda, Zhijian Huang, Tanveer Ahmed, Ping Liu, Xiangpeng Guo, David P. Ibañez, Zhiwei Luo, Meng Zhang, Mazid Md. Abdul, Zhongzhou Yang, Jiayin Yang, Yinghua Huang, Hui Zhang, Dehao Huang, Jianguo Zhou, Xiaofen Zhong, Xihua Zhu, Xiuling Fu, Wenxia Fan, Yulin Liu, Yan Xu, Carl Ward, Muhammad Jadoon Khan, Shahzina Kanwal, Bushra Mirza, Micky D. Tortorella, Hung-Fat Tse, Jiayu Chen, Baoming Qin, Xichen Bao, Shaorong Gao, Andrew P. Hutchins, Miguel A. Esteban
Publisher Correction: NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming Publisher Correction: NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming, Published online: 15 June 2018; doi:10.1038/s41556-018-0128-x Publisher Correction: NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming
HIV—No time for complacency Science (IF 37.205) Pub Date : 2018-06-15 Quarraisha Abdool Karim, Salim S. Abdool Karim
Today, the global HIV epidemic is widely viewed as triumph over tragedy. This stands in stark contrast to the first two decades of the epidemic, when AIDS was synonymous with suffering and death. But have we turned the tide on HIV sufficiently to warrant directing our attention and investments elsewhere?
News at a glance Science (IF 37.205) Pub Date : 2018-06-15 American Association for the Advancement of Science
In science news around the world, the European Commission proposes a 7-year, €94.1 billion research budget that would provide a 22% increase from the current 7-year program; but universities complain that basic research's share of the spending total would remain flat, whereas the portion for innovation would rise. Prominent cancer biologist Inder Verma resigns from the Salk Institute for Biological Studies in San Diego, California, after it investigated allegations that he sexually harassed women. Spain gets its first science minister in 7 years. NASA's new administrator, Jim Bridenstine, says he supports climate missions. And researchers report that some of Africa's oldest baobab trees are dying for unknown reasons.
Seaweed masses assault Caribbean islands Science (IF 37.205) Pub Date : 2018-06-15 Katie Langin
In 2011, massive rafts of Sargassum—a brown seaweed—washed up on beaches across the Caribbean, trapping sea turtles and filling the air with the stench of rotting eggs. The deluge was the first of its kind, but since then it has become a regular phenomenon. At first, scientists thought the seaweed drifted down from the North Atlantic's Sargasso Sea, where most Sargassum is found. But satellite imagery and data on ocean currents told a different story, revealing a new source in the tropical Atlantic Ocean. Now, scientists are scrambling to figure out what has caused the mysterious seaweed blooms.
Quantum physics could get big boost from U.S. Congress Science (IF 37.205) Pub Date : 2018-06-15 Gabriel Popkin
U.S. officials are backing an emerging effort to better organize and boost funding for quantum research, which could reshape computing, sensors, and communications. In the coming weeks, the science committee of the House of Representatives is expected to introduce legislation calling for a new, 10-year-long National Quantum Initiative. The White House and science agencies are also calling for a larger role for the federal government in quantum science. A yearlong push by a coalition of academic researchers and technology firms helped trigger this flurry of activity. Proponents argue that the United States needs a better plan for harvesting the potential fruits of quantum research—and for keeping up with global competitors.
Report details persistent hostility to women in science Science (IF 37.205) Pub Date : 2018-06-15 Meredith Wadman
A groundbreaking report on sexual harassment from the National Academies of Sciences, Engineering, and Medicine, released on 12 June, says that deep-seated, cultural change is needed to curb widespread sexual harassment of women in science. And it lays responsibility for making that change largely at the feet of leaders at academic institutions. The report says sexual harassment continues to hobble careers or even drive women from their fields—despite protective laws that have been in place for decades. To bend this curve, it says, universities need to take active measures—like transparently reporting the number of complaints they get and investigations they have underway—and insulating students by having committees advise them, to prevent them from falling under the power of a single, harassing mentor. Two years in the making, the report describes pervasive and damaging "gender harassment"—belittling behaviors intended to make women feel they don't belong, including sexist comments and demeaning jokes. In large surveys conducted at 36 campuses by two big university systems—the University of Texas and Pennsylvania State University—up to 50% of female students said they had experienced this kind of harassment, with medical students affected at the highest rates.
Seafloor fiber optic cables can listen for earthquakes Science (IF 37.205) Pub Date : 2018-06-15 Eric Hand
Some 70% of Earth's surface is covered by water, and yet nearly all earthquake detectors are on land. Aside from some expensive battery-powered sensors dropped to the sea floor and later retrieved, and a few arrays of near-shore detectors connected to land, seismologists have no way of monitoring the quakes that ripple through the sea floor and sometimes create tsunamis. Now, a technique described online in Science this week promises to take advantage of more than 1 million kilometers of fiber optic cables that crisscross the ocean floors and carry the world's internet and telecom traffic. By looking for tiny changes in an optical signal running along the cable, scientists can detect and potentially locate earthquakes. The technique requires little more than lasers at each end of the cable and access to a small portion of the cable's bandwidth. Crucially, it requires no modification to the cable itself and does not interfere with its everyday use.
Stricter Chinese student visas raise alarm Science (IF 37.205) Pub Date : 2018-06-15 Jeffrey Mervis
Reversing yet another policy of the previous administration, the U.S. Department of State this week began to apply tougher restrictions on some Chinese graduate students. The new policy shortens from 5 years to 1 year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. It will make it harder for the affected Chinese students to attend international conferences and to work collaboratively with scientists abroad, say U.S. higher education officials. It may also curtail periodic visits back home. Although the ostensible reason for the change is to improve national security, U.S. university officials see it as one more assault on graduate education and the free flow of scientific knowledge. When added to other policies by the current administration that affect non-U.S. citizens, the change may give talented foreign students one more reason to pursue advanced degrees in countries with lower barriers to entry.
Far from over Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Powerful tools exist now to stop AIDS and HIV transmission, which has led to an international push to end AIDS by 2030. But not everywhere is making progress toward that ambitious goal. A unique package of graphics looks at HIV/AIDS around the world using five different metrics: How many people are living with HIV? What is the rate of new infection? What percentage of infected people are receiving antiretroviral drugs, which both stave off disease and prevent transmission? How many infected people have progressed to AIDS and how many have died from it? And how many children are infected by their mothers? By these gauges, Nigeria, Russia, and Florida stand out from their neighbors and, in some cases, the entire world. None of these three locales has high numbers on every one of these measures. But each ranks first—an unenviable distinction—in at least one of the five metrics assessed by total cases, rates, or proportions.
The mother of all challenges Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Mother-to-child transmission (MTCT) of HIV is relatively easy to stop with antiretroviral drugs—and some countries, including the United States, have nearly eliminated it. But Nigeria has 37,000 of the 160,000 cases of MTCT that occurred in the world in 2016. The central problem is that an estimated 40% of pregnant Nigerian women never visit formal health care facilities and so do not receive HIV tests. Instead, they give birth at home with traditional birth attendants. The country has launched novel programs to test more pregnant women, including one that works with churches and another that focuses on traditional birth attendants, and then help those who test positive receive the treatment that can both prolong their lives and prevent the virus from being transmitted to their babies.
Building TRUST in an LGBTQ-hostile country Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Nigerian law makes providing services to men who have sex with men (MSM) a punishable offense. But a clinic in Abuja, run by the Institute for Human Virology, Nigeria, bills itself as "MSM friendly" and dodges the legal hurdles to test and treat this community for HIV and other sexually transmitted infections. Studies run by the clinic, which has another outpost in Lagos, have found that a startling 45% of them test positive for HIV. Official Nigerian statistics by and large ignore this community, and a recent survey of undergraduates found that 40% of them believed that health care workers should not provide services to them.
Babies who dodge HIV may not be unscathed Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Children born to HIV-positive mothers who do not become infected themselves may still suffer some health problems, such as delayed growth and immune abnormalities. A research project in Benin City run by the Institute for Human Virology, Nigeria, is attempting to assess whether exposure to the virus—or to antiretroviral drugs taken by the mother and baby that thwart transmission—may cause harm. It's difficult to separate out the many confounding variables that could lead to problems in HIV-negative babies, including the compromised health of the mothers. But the study hopes to clarify these issues by comparing 300 exposed and unexposed infants and their mothers during their first 2 years of life.
Dark nights, bright stars Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
At a time when HIV epidemics in Western Europe are shrinking, Russia's is growing by about 10% a year. Russia, in fact, between 2010 and 2015 accounted for more than 80% of all the new infections in Eastern Europe and Central Asia. Not only has the country turned away assistance from The Global Fund to Fight AIDS, Tuberculosis and Malaria, it also has refused to adopt scientifically proven strategies to slow spread between people who inject drugs, the community that kicked off the Russian epidemic. Only about one in three of the estimated 1 million Russians living with HIV have access to antiretroviral drugs, which means that the country doesn't receive much benefit on a population level from what's known as treatment as prevention. But there are signs in St. Petersburg that its unusually progressive response—by Russian standards—is beginning to turn things around.
Status symbol Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Pavel Lobkov, a well-known anchor on the news station TV Rain, in 2015 took an action that few prominent Russians have dared to take: He went public with the fact that he is living with HIV. Stigma and discrimination against HIV-infected people still runs high in Russia, leading many to avoid getting tested and, in turn, preventing them from receiving the treatment they need both to prevent AIDS and to lower the chance of them transmitting the virus to others. Lobkov says many people reached out to him after he went public with his HIV status because he demonstrated that you could lead a normal, healthy life even if you're infected.
Poster couple Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Tatiana Vinogradova, deputy director of St. Petersburg's AIDS center, is married to an HIV-positive man, Andrey Skvortsov. Many couples of course have "discordant" HIV status, but because Vinogradova is a leader in the city's response to the epidemic and Skvortsov is a well-known patient advocate, they agreed to appear on a poster that told their story, in the hopes of convincing others that there's no reason to fear HIV-infected people. They also want to reduce bias and fear in the medical community, as many doctors, dentists, and other professionals still shy away from offering care to people who are living with HIV.
The pill exchange Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Alexander Chebin of Yekaterinburg and Yulia Vereschagina of St. Petersburg live more than 1000 kilometers away from each other, but they work together sharing antiretroviral drugs, which they then distribute to people in need. Their "reserve pharmacy" is an underground network that collects the drugs from people who switch regimens or die, and distributes them to people who have trouble accessing the life-saving medication because of bureaucratic hurdles or the occasional "stock-outs" that occur in official government pharmacies. People find them through social media websites, and they distribute the drugs free of charge.
The loyal opposition Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Russian government officials who speak critically about their leadership often find themselves out of a job—or worse. Vadim Pokrovsky, who heads the Federal Center for the Prevention and Control of the Spread of AIDS in Moscow, blasts his government for its lackluster response to HIV/AIDS and even says Ministry of Health officials routinely play down the epidemic's severity. Pokrovsky says the Russian Orthodox Church holds too much sway, and he thinks the federal government needs to provide much more substantial funding if it hopes to slow the rampant spread of HIV and help more infected people. And for whatever reason, the government tolerates this lone official voice of dissent.
The Sunshine State's dark cloud Science (IF 37.205) Pub Date : 2018-06-15 Jon Cohen
Miami in 2016 was in first place on the list that ranks U.S. cities by new HIV diagnoses. And three other cities in Florida were also on the list. Florida also has more cases of AIDS than any state. The problem is complex, and it differs in the cities and rural areas. Miami has a terrifically diverse community with many immigrants from other countries that cannot be reached with a one-size-fits-all message or outreach efforts. Rural Florida is in the heart of the conservative Bible Belt in the deep South, which is famously homophobic and looks askance at sexual education. New efforts are underway to try to improve the situation in Florida by squarely looking its shortcomings in the eye and confronting them one by one.
A tool for finding rare marine species Science (IF 37.205) Pub Date : 2018-06-15 Ellen K. Pikitch
By their very nature, rare marine species are challenging to study. They often elude detection by established research methods because of their scarcity and patchy distribution. Their small populations demand the use of sampling techniques that minimize the risks of injury or death and that conserve the habitats and ecological communities that support them. At the same time, ever more once-common marine species are becoming rare as threats such as overfishing, invasive species, and environmental destruction reduce their abundance (1). Analysis of environmental DNA (eDNA) shows promise as a rapid, safe, sensitive, and cost-effective means for detecting and studying rare marine species.
Crystallizing a memory Science (IF 37.205) Pub Date : 2018-06-15 Steve Ramirez
What is the physical basis of memory? What does it take to retrieve a memory in the brain? What would it take to activate or erase memories? In the early 20th century, the German zoologist Richard Semon coined the term “engram” to denote the physical manifestation of a memory in the brain (1). Two decades later, Canadian psychologist Donald Hebb posited a physiological correlate for learning and recollection: The process of learning strengthens the connections, or synapses, between neurons, which leads to the development of brain-wide cell assemblies that undergo changes in their structural and functional connectivity (2). The coordinated activity of these assemblies—called ensembles, traces, or engrams—that occurs during learning (memory formation) is thought to be reengaged during recall and thereby forms a stable neuronal correlate of memory (2). As subsequent memories are formed, the dynamics of these assemblies evolve and provide preexisting scaffolds to influence how the brain processes the variety of memories an organism forms. Studies by Abdou et al. (3) on page 1227 of this issue and by Choi et al. (4) develop new technologies to visualize discrete engrams in the brain and modulate them in a synapse-specific manner to understand memory strength and memory restoration from an amnestic state. This improved understanding could eventually be translated to modulate memories to alleviate maladaptive memory states.
Scaling of human brain size Science (IF 37.205) Pub Date : 2018-06-15 David C. Van Essen
What makes humans unique as a species and as individuals? Our uniqueness stems from language, tool use, reasoning, and other cognitive abilities that are largely mediated by specialized regions of the cerebral cortex. These regions of higher cognitive function have expanded disproportionately during human evolution (compared with nonhuman primates) and during postnatal maturation, when cortical surface area expands threefold between infancy and adulthood (1). Our uniqueness as individuals reflects countless differences in brain structure, function, and connectivity. One basic anatomical difference between similarly aged individuals is a more than 1.5-fold variation in total brain size (and total cortical volume) (2). On page 1222 of this issue, Reardon et al. (3) bring this aspect of individual variability under the umbrella of “differential scaling” by showing that human brains of different sizes do not scale uniformly across all regions. Rather, larger brains show greater expansion in regions associated with higher cognition and less expansion in regions associated with sensory, motor, and limbic (emotion- and affect-related) functions.
Animals feel safer from humans in the dark Science (IF 37.205) Pub Date : 2018-06-15 Ana Benítez-López
About 75% of Earth's land surface is currently modified by human activities (1). The expanding footprint of human activities is not only causing the loss of habitat and biodiversity but also affecting the dynamics of wildlife populations. Researchers have long examined human-induced spatial shifts in the distribution of wildlife, but temporal adjustments in animal activity have received less attention. On page 1232 of this issue, Gaynor et al. (2) present a comprehensive meta-analysis to quantify the increase in wildlife nocturnality due to human disturbance.
Facing your fears Science (IF 37.205) Pub Date : 2018-06-15 Paul W. Frankland, Sheena A. Josselyn
Remembering traumatic fearful events is adaptive. However, treating no-longer-threatening situations as dangerous may be maladaptive and lead to anxiety disorders, including phobias and posttraumatic stress disorder. Central to many forms of therapy designed to tackle these anxiety disorders is the idea that to overcome fear, one needs to face it. For instance, cognitive behavioral therapy and exposure therapy allow patients to confront the objects or situations that provoke their anxiety in the controlled environment of the therapist's office. With repeated exposures, the patients' anxiety levels gradually decline, and the objects or situations that they once feared no longer trouble them. On page 1239 of this issue Khalaf et al. (1) provide a neural mechanism in mice for “facing one's fears.” These findings may inform the development of more effective forms of treatment for anxiety disorders.
Understanding spatial environments from images Science (IF 37.205) Pub Date : 2018-06-15 Matthias Zwicker
The ability to understand spatial environments based on visual perception arguably is a key function of the cognitive system of many animals, including mammalians and others. A common presumption about artificial intelligence is that its goal is to build machines with a similar capacity of “understanding.” The research community in artificial intelligence, however, has settled on a more pragmatic approach. Instead of attempting to model or quantify understanding directly, the objective is to construct machines that merely solve tasks that seem to require understanding. Understanding can only be measured indirectly, for example, by analyzing the ability of a system to generalize the solving of new tasks, which is sometimes called transfer learning (1). Transfer learning is particularly appealing in an unsupervised setting, which means that the objective of the original task is defined in terms of the input data itself, without requiring additional, task-specific information (see the figure). On page 1204 of this issue, Eslami et al. (2) present an important step toward building machines that learn to understand spatial environments using unsupervised transfer learning. Remarkably, they develop a system that relies only on inputs from its own image sensors, and that learns autonomously and without human supervision.
Preparing ocean governance for species on the move Science (IF 37.205) Pub Date : 2018-06-15 Malin L. Pinsky, Gabriel Reygondeau, Richard Caddell, Juliano Palacios-Abrantes, Jessica Spijkers, William W. L. Cheung
The ocean is a critical source of nutrition for billions of people, with potential to yield further food, profits, and employment in the future (1). But fisheries face a serious new challenge as climate change drives the ocean to conditions not experienced historically. Local, national, regional, and international fisheries are substantially underprepared for geographic shifts in marine animals driven by climate change over the coming decades. Fish and other animals have already shifted into new territory at a rate averaging 70 km per decade (2), and these shifts are expected to continue or accelerate (3). We show here that many species will likely shift across national and other political boundaries in the coming decades, creating the potential for conflict over newly shared resources.
Asperger's chilling complicity Science (IF 37.205) Pub Date : 2018-06-15 Meredith Wadman
With the growing prominence of Asperger's syndrome has come increased scrutiny of the man behind it. But until recently, historians writing in English have either skirted Asperger's closeness to the Nazi regime or depicted him as a compassionate physician who used his medical position to rescue disabled children otherwise bound for destruction. The 2016 book In a Different Key: The Story of Autism, by John Donvan and Caren Zucker, began to dismantle this portrait of Asperger. In her new book, Asperger's Children, Edith Sheffer finishes the job.
Platforms of power Science (IF 37.205) Pub Date : 2018-06-15 Anna Lauren Hoffmann
In Custodians of the Internet, Tarleton Gillespie goes beyond a mere account of the tools and practices employed by social media companies to address problems of harassment, obscenity, and hate speech on their platforms. He also aims to capture just what is at stake in debates over online expression—from the consequences of being "censored" online to the fate of social and democratic norms in the face of easily manipulable news feeds.
Neural scene representation and rendering Science (IF 37.205) Pub Date : 2018-06-15 S. M. Ali Eslami, Danilo Jimenez Rezende, Frederic Besse, Fabio Viola, Ari S. Morcos, Marta Garnelo, Avraham Ruderman, Andrei A. Rusu, Ivo Danihelka, Karol Gregor, David P. Reichert, Lars Buesing, Theophane Weber, Oriol Vinyals, Dan Rosenbaum, Neil Rabinowitz, Helen King, Chloe Hillier, Matt Botvinick, Daan Wierstra, Koray Kavukcuoglu, Demis Hassabis
Scene representation—the process of converting visual sensory data into concise descriptions—is a requirement for intelligent behavior. Recent work has shown that neural networks excel at this task when provided with large, labeled datasets. However, removing the reliance on human labeling remains an important open problem. To this end, we introduce the Generative Query Network (GQN), a framework within which machines learn to represent scenes using only their own sensors. The GQN takes as input images of a scene taken from different viewpoints, constructs an internal representation, and uses this representation to predict the appearance of that scene from previously unobserved viewpoints. The GQN demonstrates representation learning without human labels or domain knowledge, paving the way toward machines that autonomously learn to understand the world around them.
Photochemistry beyond the red limit in chlorophyll f–containing photosystems Science (IF 37.205) Pub Date : 2018-06-15 Dennis J. Nürnberg, Jennifer Morton, Stefano Santabarbara, Alison Telfer, Pierre Joliot, Laura A. Antonaru, Alexander V. Ruban, Tanai Cardona, Elmars Krausz, Alain Boussac, Andrea Fantuzzi, A. William Rutherford
Photosystems I and II convert solar energy into the chemical energy that powers life. Chlorophyll a photochemistry, using red light (680 to 700 nm), is near universal and is considered to define the energy “red limit” of oxygenic photosynthesis. We present biophysical studies on the photosystems from a cyanobacterium grown in far-red light (750 nm). The few long-wavelength chlorophylls present are well resolved from each other and from the majority pigment, chlorophyll a. Charge separation in photosystem I and II uses chlorophyll f at 745 nm and chlorophyll f (or d) at 727 nm, respectively. Each photosystem has a few even longer-wavelength chlorophylls f that collect light and pass excitation energy uphill to the photochemically active pigments. These photosystems function beyond the red limit using far-red pigments in only a few key positions.
Giant tunneling magnetoresistance in spin-filter van der Waals heterostructures Science (IF 37.205) Pub Date : 2018-06-15 Tiancheng Song, Xinghan Cai, Matisse Wei-Yuan Tu, Xiaoou Zhang, Bevin Huang, Nathan P. Wilson, Kyle L. Seyler, Lin Zhu, Takashi Taniguchi, Kenji Watanabe, Michael A. McGuire, David H. Cobden, Di Xiao, Wang Yao, Xiaodong Xu
Magnetic multilayer devices that exploit magnetoresistance are the backbone of magnetic sensing and data storage technologies. Here, we report multiple-spin-filter magnetic tunnel junctions (sf-MTJs) based on van der Waals (vdW) heterostructures in which atomically thin chromium triiodide (CrI3) acts as a spin-filter tunnel barrier sandwiched between graphene contacts. We demonstrate tunneling magnetoresistance that is drastically enhanced with increasing CrI3 layer thickness, reaching a record 19,000% for magnetic multilayer structures using four-layer sf-MTJs at low temperatures. Using magnetic circular dichroism measurements, we attribute these effects to the intrinsic layer-by-layer antiferromagnetic ordering of the atomically thin CrI3. Our work reveals the possibility to push magnetic information storage to the atomically thin limit and highlights CrI3 as a superlative magnetic tunnel barrier for vdW heterostructure spintronic devices.
Probing magnetism in 2D van der Waals crystalline insulators via electron tunneling Science (IF 37.205) Pub Date : 2018-06-15 D. R. Klein, D. MacNeill, J. L. Lado, D. Soriano, E. Navarro-Moratalla, K. Watanabe, T. Taniguchi, S. Manni, P. Canfield, J. Fernández-Rossier, P. Jarillo-Herrero
Magnetic insulators are a key resource for next-generation spintronic and topological devices. The family of layered metal halides promises varied magnetic states, including ultrathin insulating multiferroics, spin liquids, and ferromagnets, but device-oriented characterization methods are needed to unlock their potential. Here, we report tunneling through the layered magnetic insulator CrI3 as a function of temperature and applied magnetic field. We electrically detect the magnetic ground state and interlayer coupling and observe a field-induced metamagnetic transition. The metamagnetic transition results in magnetoresistances of 95, 300, and 550% for bilayer, trilayer, and tetralayer CrI3 barriers, respectively. We further measure inelastic tunneling spectra for our junctions, unveiling a rich spectrum consistent with collective magnetic excitations (magnons) in CrI3.
Normative brain size variation and brain shape diversity in humans Science (IF 37.205) Pub Date : 2018-06-15 P. K. Reardon, Jakob Seidlitz, Simon Vandekar, Siyuan Liu, Raihaan Patel, Min Tae M. Park, Aaron Alexander-Bloch, Liv S. Clasen, Jonathan D. Blumenthal, Francois M. Lalonde, Jay N. Giedd, Ruben C. Gur, Raquel E. Gur, Jason P. Lerch, M. Mallar Chakravarty, Theodore D. Satterthwaite, Russell T. Shinohara, Armin Raznahan
Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.
Synapse-specific representation of the identity of overlapping memory engrams Science (IF 37.205) Pub Date : 2018-06-15 Kareem Abdou, Mohammad Shehata, Kiriko Choko, Hirofumi Nishizono, Mina Matsuo, Shin-ichi Muramatsu, Kaoru Inokuchi
Memories are integrated into interconnected networks; nevertheless, each memory has its own identity. How the brain defines specific memory identity out of intermingled memories stored in a shared cell ensemble has remained elusive. We found that after complete retrograde amnesia of auditory fear conditioning in mice, optogenetic stimulation of the auditory inputs to the lateral amygdala failed to induce memory recall, implying that the memory engram no longer existed in that circuit. Complete amnesia of a given fear memory did not affect another linked fear memory encoded in the shared ensemble. Optogenetic potentiation or depotentiation of the plasticity at synapses specific to one memory affected the recall of only that memory. Thus, the sharing of engram cells underlies the linkage between memories, whereas synapse-specific plasticity guarantees the identity and storage of individual memories.
The influence of human disturbance on wildlife nocturnality Science (IF 37.205) Pub Date : 2018-06-15 Kaitlyn M. Gaynor, Cheryl E. Hojnowski, Neil H. Carter, Justin S. Brashares
Rapid expansion of human activity has driven well-documented shifts in the spatial distribution of wildlife, but the cumulative effect of human disturbance on the temporal dynamics of animals has not been quantified. We examined anthropogenic effects on mammal diel activity patterns, conducting a meta-analysis of 76 studies of 62 species from six continents. Our global study revealed a strong effect of humans on daily patterns of wildlife activity. Animals increased their nocturnality by an average factor of 1.36 in response to human disturbance. This finding was consistent across continents, habitats, taxa, and human activities. As the global human footprint expands, temporal avoidance of humans may facilitate human-wildlife coexistence. However, such responses can result in marked shifts away from natural patterns of activity, with consequences for fitness, population persistence, community interactions, and evolution.
Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Science (IF 37.205) Pub Date : 2018-06-15 Lorenzo Caputi, Jakob Franke, Scott C. Farrow, Khoa Chung, Richard M. E. Payne, Trinh-Don Nguyen, Thu-Thuy T. Dang, Inês Soares Teto Carqueijeiro, Konstantinos Koudounas, Thomas Dugé de Bernonville, Belinda Ameyaw, D. Marc Jones, Ivo Jose Curcino Vieira, Vincent Courdavault, Sarah E. O’Connor
Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds.
Reactivation of recall-induced neurons contributes to remote fear memory attenuation Science (IF 37.205) Pub Date : 2018-06-15 Ossama Khalaf, Siegfried Resch, Lucie Dixsaut, Victoire Gorden, Liliane Glauser, Johannes Gräff
Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found—chemogenetically and in an engram-specific manner—that effective remote fear attenuation is accompanied by the reactivation of memory recall–induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction. This suggests that the original memory trace of fear actively contributes to remote fear attenuation.
Near-atomic model of microtubule-tau interactions Science (IF 37.205) Pub Date : 2018-06-15 Elizabeth H. Kellogg, Nisreen M. A. Hejab, Simon Poepsel, Kenneth H. Downing, Frank DiMaio, Eva Nogales
Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer’s disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo–electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces.
Ghost cytometry Science (IF 37.205) Pub Date : 2018-06-15 Sadao Ota, Ryoichi Horisaki, Yoko Kawamura, Masashi Ugawa, Issei Sato, Kazuki Hashimoto, Ryosuke Kamesawa, Kotaro Setoyama, Satoko Yamaguchi, Katsuhito Fujiu, Kayo Waki, Hiroyuki Noji
Ghost imaging is a technique used to produce an object’s image without using a spatially resolving detector. Here we develop a technique we term “ghost cytometry,” an image-free ultrafast fluorescence “imaging” cytometry based on a single-pixel detector. Spatial information obtained from the motion of cells relative to a static randomly patterned optical structure is compressively converted into signals that arrive sequentially at a single-pixel detector. Combinatorial use of the temporal waveform with the intensity distribution of the random pattern allows us to computationally reconstruct cell morphology. More importantly, we show that applying machine-learning methods directly on the compressed waveforms without image reconstruction enables efficient image-free morphology-based cytometry. Despite a compact and inexpensive instrumentation, image-free ghost cytometry achieves accurate and high-throughput cell classification and selective sorting on the basis of cell morphology without a specific biomarker, both of which have been challenging to accomplish using conventional flow cytometers.
Technology Feature | Translating big data: The proteomics challenge Science (IF 37.205) Pub Date : 2018-06-15 Mike May
Getting the most out of protein-related information depends on teamwork among scientists around the world, and that involves sharing large datasets. Simply passing big data back and forth is not a problem, however—the main obstacle is sharing that data in a way that other scientists can use it. Building software that can interpret information from different experiments and equipment remains complicated; likewise, exploring and analyzing large datasets from proteomics experiments even from one lab requires software that is most often developed in-house. Read the Feature (Full-Text HTML)Read the Feature (PDF)Read New Products (PDF)
Induction of CD4 T cell memory by local cellular collectivity Science (IF 37.205) Pub Date : 2018-06-15 Michal Polonsky, Jacob Rimer, Amos Kern-Perets, Irina Zaretsky, Stav Miller, Chamutal Bornstein, Eyal David, Naama Meira Kopelman, Gil Stelzer, Ziv Porat, Benjamin Chain, Nir Friedman
Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4+ T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses.
Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases Science (IF 37.205) Pub Date : 2018-06-15 Arnaud Pommier, Naishitha Anaparthy, Nicoletta Memos, Z. Larkin Kelley, Alizée Gouronnec, Ran Yan, Cédric Auffray, Jean Albrengues, Mikala Egeblad, Christine A. Iacobuzio-Donahue, Scott K. Lyons, Douglas T. Fearon
The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intraportal injection of immunogenic PDA cells into preimmunized mice seeded livers only with single, nonreplicating DCCs that were CK19– and MHCI–. The DCCs exhibited an endoplasmic reticulum (ER) stress response but paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s). Inducible expression of XBP1s in DCCs, in combination with T cell depletion, stimulated the outgrowth of macrometastatic lesions that expressed CK19 and MHCI. Thus, unresolved ER stress enables DCCs to escape immunity and establish latent metastases.
Improving mechanical sensor performance through larger damping Science (IF 37.205) Pub Date : 2018-06-15 Swapan K. Roy, Vincent T. K. Sauer, Jocelyn N. Westwood-Bachman, Anandram Venkatasubramanian, Wayne K. Hiebert
Mechanical resonances are used in a wide variety of devices, from smartphone accelerometers to computer clocks and from wireless filters to atomic force microscopes. Frequency stability, a critical performance metric, is generally assumed to be tantamount to resonance quality factor (the inverse of the linewidth and of the damping). We show that the frequency stability of resonant nanomechanical sensors can be improved by lowering the quality factor. At high bandwidths, quality-factor reduction is completely mitigated by increases in signal-to-noise ratio. At low bandwidths, notably, increased damping leads to better stability and sensor resolution, with improvement proportional to damping. We confirm the findings by demonstrating temperature resolution of 60 microkelvin at 300-hertz bandwidth. These results open the door to high-performance ultrasensitive resonators in gaseous or liquid environments, single-cell nanocalorimetry, nanoscale gas chromatography, atmospheric-pressure nanoscale mass spectrometry, and new approaches in crystal oscillator stability.
Comment on “Satellites reveal contrasting responses of regional climate to the widespread greening of Earth” Science (IF 37.205) Pub Date : 2018-06-15 Yue Li, Zhenzhong Zeng, Ling Huang, Xu Lian, Shilong Piao
Forzieri et al. (Reports, 16 June 2017, p. 1180) used satellite data to show that boreal greening caused regional warming. We show that this positive sensitivity of temperature to the greening can be derived from the positive response of vegetation to boreal warming, which indicates that results from a statistical regression with satellite data should be carefully interpreted.
Response to Comment on “Satellites reveal contrasting responses of regional climate to the widespread greening of Earth” Science (IF 37.205) Pub Date : 2018-06-15 Giovanni Forzieri, Ramdane Alkama, Diego G. Miralles, Alessandro Cescatti
Li et al. contest the idea that vegetation greening has contributed to boreal warming and argue that the sensitivity of temperature to leaf area index (LAI) is instead likely driven by the climate impact on vegetation. We provide additional evidence that the LAI-climate interplay is indeed largely driven by the vegetation impact on temperature and not vice versa, thus corroborating our original conclusions.
Ultrastable laser interferometry for earthquake detection with terrestrial and submarine cables Science (IF 37.205) Pub Date : 2018-06-14 Giuseppe Marra, Cecilia Clivati, Richard Luckett, Anna Tampellini, Jochen Kronjäger, Louise Wright, Alberto Mura, Filippo Levi, Stephen Robinson, André Xuereb, Brian Baptie, Davide Calonico
Detecting ocean-floor seismic activity is crucial for our understanding of the interior structure and dynamic behavior of the Earth. However, 70% of the planet’s surface is covered by water and seismometers coverage is limited to a handful of permanent ocean bottom stations. We show that existing telecommunication optical fiber cables can detect seismic events when combined with state-of-the-art frequency metrology techniques by using the fiber itself as the sensing element. We detected earthquakes over terrestrial and submarine links with length ranging from 75 to 535 km and a geographical distance from the earthquake's epicenter ranging from 25 to 18,500 km. Implementing a global seismic network for real-time detection of underwater earthquakes requires applying the proposed technique to the existing extensive submarine optical fiber network.
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser Science (IF 37.205) Pub Date : 2018-06-14 Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Båth, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss
Ultrafast isomerization of retinal is the primary step in photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an x-ray laser. A series of structural snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a twisted geometry and emerging in the 13-cis conformation. Our findings suggest ultrafast collective motions of aspartic acid residues and functional water molecules in the proximity of the retinal Schiff base as a key ingredient for this stereo-selective and efficient photochemical reaction.
Sex reversal following deletion of a single distal enhancer of Sox9 Science (IF 37.205) Pub Date : 2018-06-14 Nitzan Gonen, Chris R. Futtner, Sophie Wood, S. Alexandra Garcia-Moreno, Isabella M. Salamone, Shiela C. Samson, Ryohei Sekido, Francis Poulat, Danielle M. Maatouk, Robin Lovell-Badge
Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9. Although others are redundant, Enh13, a 557–base pair element located 565 kilobases 5′, is essential to initiate mouse testis development; its deletion giving XY females with Sox9 transcript levels equivalent to XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in patients is associated with XY sex reversal, suggesting it is also critical in humans.
The South Asian monsoon—Pollution pump and purifier Science (IF 37.205) Pub Date : 2018-06-14 J. Lelieveld, E. Bourtsoukidis, C. Brühl, H. Fischer, H. Fuchs, H. Harder, A. Hofzumahaus, F. Holland, D. Marno, M. Neumaier, A. Pozzer, H. Schlager, J. Williams, A. Zahn, H. Ziereis
Air pollution is growing fastest in monsoon-impacted South Asia. During the dry, winter monsoon the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet, summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the “Oxidation Mechanism Observations” campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism in which contaminants are rapidly oxidized and deposited to Earth’s surface. However, some pollutants are lofted above the monsoon clouds, and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.
Dirac-source field-effect transistors as energy-efficient, high-performance electronic switches Science (IF 37.205) Pub Date : 2018-06-14 Chenguang Qiu, Fei Liu, Lin Xu, Bing Deng, Mengmeng Xiao, Jia Si, Li Lin, Zhiyong Zhang, Jian Wang, Hong Guo, Hailin Peng, Lian-Mao Peng
An efficient way to reduce the power is to lower the supply voltage VDD, but this voltage is restricted by the 60 millivolts per decade thermionic limit of subthreshold swing (SS) in field-effect transistors (FETs). We show that a graphene Dirac source (DS) with a much narrower electron density distribution around the Fermi level than that of conventional FETs can lower SS. A DS-FET with a carbon nanotube channel provided an average SS of 40 millivolt per decade over four decades of current at room temperature and high device current I60 of up to 40 microampere per micrometer at 60 millivolts per decade. When compared with state-of-the-art Si 14-nanometer node FETs, a similar Ion is realized but at much lower supply voltage of 0.5 versus 0.7 volts for Si, and a much steeper SS below 35 millivolts per decade in the off-state.
A dust-enshrouded tidal disruption event with a resolved radio jet in a galaxy merger Science (IF 37.205) Pub Date : 2018-06-14 S. Mattila, M. Pérez-Torres, A. Efstathiou, P. Mimica, M. Fraser, E. Kankare, A. Alberdi, M. Á. Aloy, T. Heikkilä, P. G. Jonker, P. Lundqvist, I. Martí-Vidal, W. P. S. Meikle, C. Romero-Cañizales, S. J. Smartt, S. Tsygankov, E. Varenius, A. Alonso-Herrero, M. Bondi, C. Fransson, R. Herrero-Illana, T. Kangas, R. Kotak, N. Ramírez-Olivencia, P. Väisänen, R. J. Beswick, D. L. Clements, R. Greimel, J. Harmanen, J. Kotilainen, K. Nandra, T. Reynolds, S. Ryder, N. A. Walton, K. Wiik, G. Östlin
Tidal disruption events (TDEs) are transient flares produced when a star is ripped apart by the gravitational field of a supermassive black hole (SMBH). We have observed a transient source in the western nucleus of the merging galaxy pair Arp 299 that radiated >1.5 × 1052 erg in the infrared and radio but was not luminous at optical or x-ray wavelengths. We interpret this as a TDE with much of its emission reradiated at infrared wavelengths by dust. Efficient reprocessing by dense gas and dust may explain the difference between theoretical predictions and observed luminosities of TDEs. The radio observations resolve an expanding and decelerating jet, probing the jet formation and evolution around a SMBH.
History by the numbers? [Letters (Online Only)] PNAS (IF 9.661) Pub Date : 2018-06-14 Nick Tosh, John Ferguson, Cathal Seoighe
Turchin et al.’s (1) “Global History Databank” is an exciting project. However, we are not convinced that their principal component analysis (PCA) succeeds in discriminating between competing historical hypotheses. We also have concerns about their missing data imputation strategy.
Reply to Tosh et al.: Quantitative analyses of cultural evolution require engagement with historical and archaeological research [Letters (Online Only)] PNAS (IF 9.661) Pub Date : 2018-06-14 Thomas E. Currie, Peter Turchin, Harvey Whitehouse, Pieter François, Kevin Feeney, Daniel Mullins, Daniel Hoyer, Christina Collins, Stephanie Grohmann, Patrick Savage, Gavin Mendel-Gleason, Edward Turner, Agathe Dupeyron, Enrico Cioni, Jenny Reddish, Jill Levine, Greine Jordan, Eva Brandl, Alice Williams, Rudolf Cesaretti, Marta Krueger, Alessandro Ceccarelli, Joe Figliulo-Rosswurm, Po-Ju Tuan, Peter Peregrine, Arkadiusz Marciniak, Johannes Preiser-Kapeller, Nikolay Kradin, Andrey Korotayev, Alessio Palmisano, David Baker, Julye Bidmead, Peter Bol, David Christian, Connie Cook, Alan Covey, Gary Feinman, Árni Daníel Júlíusson, Axel Kristinsson, John Miksic, Ruth Mostern, Cameron Petrie, Peter Rudiak-Gould, Barend ter Haar, Vesna Wallace, Victor Mair, Liye Xie, John Baines, Elizabeth Bridges, Joseph Manning, Bruce Lockhart, Amy Bogaard, Charles Spencer
We thank Tosh et al. (1) for their interest in our research (2) but note that their analyses do not undermine the main findings of our article. Their suggestion that polity population divided by polity area should be one of the social complexity dimensions raises a number of issues. What does this ratio mean at large spatial scales, where populations are concentrated in large urban centers and much of the territory is not heavily populated? How are societies distributed across this variable and why? For example, a small-scale “simple” society could have a very high population density if it has access to a rich resource base. Tosh et al. (1) do not provide sufficient information or context to meaningfully …
Payments for environmental services supported social capital while increasing land management [Sustainability Science] PNAS (IF 9.661) Pub Date : 2018-06-14 Jennifer M. Alix-Garcia, Katharine R. E. Sims, Victor H. Orozco-Olvera, Laura E. Costica, Jorge David Fernández Medina, Sofía Romo Monroy
Payments for environmental services (PES) programs incentivize landowners to protect or improve natural resources. Many conservationists fear that introducing compensation for actions previously offered voluntarily will reduce social capital (the institutions, relationships, attitudes, and values that govern human interactions), yet little rigorous research has investigated this concern. We examined the land cover management and communal social capital impacts of Mexico’s federal conservation payments program, which is a key example for other countries committed to reducing deforestation, protecting watersheds, and conserving biodiversity. We used a regression discontinuity (RD) methodology to identify causal program effects, comparing outcomes for PES participants and similar rejected applicants close to scoring cutoffs. We found that payments increased land cover management activities, such as patrolling for illegal activity, building fire breaks, controlling pests, or promoting soil conservation, by ∼50%. Importantly, increases in paid activities as a result of PES did not crowd out unpaid contributions to land management or other prosocial work. Community social capital increased by ∼8–9%, and household-level measures of trust were not affected by the program. These findings demonstrate that major environmental conditional cash transfer programs can support both land management and the attitudes and institutions underpinning prosocial behavior. Rigorous empirical research on this question can proceed only country by country because of methodological limitations, but will be an important line of inquiry as PES continues to expand worldwide.
Distribution and functional analysis of the phosphopantetheinyl transferase superfamily in Actinomycetales microorganisms [Microbiology] PNAS (IF 9.661) Pub Date : 2018-06-14 Jeong Ho Kim, Mamoru Komatsu, Kazuo Shin-ya, Satoshi Omura, Haruo Ikeda
Phosphopantetheinyl transferases (PPTases) are a superfamily of essential enzymes required for the synthetic processes of many compounds including fatty acid, polyketide, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways via the transfer of a phosphopantetheinyl moiety to a serine residue in the conserved motif of carrier proteins. Since many Actinomycetales microorganisms produce a number of polyketide and nonribosomal peptide metabolites, the distribution of PPTase genes was investigated in these microorganisms. PPTases were found in bacterial protein databases using a hidden Markov model search with the PF01648 (4′-phosphopantetheinyl transferase superfamily) model. Actinomycetales microorganisms harbor several genes encoding AcpS-type and Sfp-type PPTases in individual genomes, many of which were associated with the biosynthetic gene cluster for polyketide or nonribosomal peptide metabolites. The properties of these PPTases were evaluated in the heterologous expression system using the biosynthetic gene clusters and genes encoding PPTases found in the present study. Sfp-type PPTases were classified into two subgroups, and although the substrate specificities of the enzymes in one subgroup were wide, the catalytic activities of enzymes in the other subgroup were low. SAV_1784 of Streptomyces avermitilis possessed the most characteristic broad-range activity against several type I polyketide synthases and nonribosomal peptide synthetases.
Loss of coral reef growth capacity to track future increases in sea level Nature (IF 40.137) Pub Date : 2018-06-14 Chris T. Perry, Lorenzo Alvarez-Filip, Nicholas A. J. Graham, Peter J. Mumby, Shaun K. Wilson, Paul S. Kench, Derek P. Manzello, Kyle M. Morgan, Aimee B. A. Slangen, Damian P. Thomson, Fraser Januchowski-Hartley, Scott G. Smithers, Robert S. Steneck, Renee Carlton, Evan N. Edinger, Ian C. Enochs, Nuria Estrada-Saldívar, Michael D. E. Haywood, Graham Kolodziej, Gary N. Murphy, Esmeralda Pérez-Cervantes, Adam Suchley, Lauren Valentino, Robert Boenish, Margaret Wilson, Chancey Macdonald
AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells Cell Stem Cell (IF 23.394) Pub Date : 2018-06-14 Shanshan Pei, Mohammad Minhajuddin, Biniam Adane, Nabilah Khan, Brett M. Stevens, Stephen C. Mack, Sisi Lai, Jeremy N. Rich, Anagha Inguva, Kevin M. Shannon, Hyunmin Kim, Aik-Choon Tan, Jason R. Myers, John M. Ashton, Tobias Neff, Daniel A. Pollyea, Clayton A. Smith, Craig T. Jordan
Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency Cell Stem Cell (IF 23.394) Pub Date : 2018-06-14 Kenjiro Adachi, Wolfgang Kopp, Guangming Wu, Sandra Heising, Boris Greber, Martin Stehling, Marcos J. Araúzo-Bravo, Stefan T. Boerno, Bernd Timmermann, Martin Vingron, Hans R. Schöler
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