Showing papers in "Proceedings of the National Academy of Sciences of the United States of America in 2015"
TL;DR: The first global map (228 countries) of antibiotic consumption in livestock is presented and it is projected that antimicrobial consumption will rise by 67% by 2030, and nearly double in Brazil, Russia, India, China, and South Africa.
Abstract: Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.
2,371 citations
TL;DR: A marked increase in the all-cause mortality of middle-aged white non-Hispanic men and women in the United States between 1999 and 2013 reversed decades of progress in mortality and was unique to the United United States; no other rich country saw a similar turnaround.
Abstract: This paper documents a marked increase in the all-cause mortality of middle-aged white non-Hispanic men and women in the United States between 1999 and 2013. This change reversed decades of progress in mortality and was unique to the United States; no other rich country saw a similar turnaround. The midlife mortality reversal was confined to white non-Hispanics; black non-Hispanics and Hispanics at midlife, and those aged 65 and above in every racial and ethnic group, continued to see mortality rates fall. This increase for whites was largely accounted for by increasing death rates from drug and alcohol poisonings, suicide, and chronic liver diseases and cirrhosis. Although all education groups saw increases in mortality from suicide and poisonings, and an overall increase in external cause mortality, those with less education saw the most marked increases. Rising midlife mortality rates of white non-Hispanics were paralleled by increases in midlife morbidity. Self-reported declines in health, mental health, and ability to conduct activities of daily living, and increases in chronic pain and inability to work, as well as clinically measured deteriorations in liver function, all point to growing distress in this population. We comment on potential economic causes and consequences of this deterioration.
1,858 citations
TL;DR: Dynamic changes observed during microbiome acquisition, as well as steady-state compositions of spatial compartments, support a multistep model for root microbiome assembly from soil wherein the rhizoplane plays a selective gating role.
Abstract: Plants depend upon beneficial interactions between roots and microbes for nutrient availability, growth promotion, and disease suppression. High-throughput sequencing approaches have provided recent insights into root microbiomes, but our current understanding is still limited relative to animal microbiomes. Here we present a detailed characterization of the root-associated microbiomes of the crop plant rice by deep sequencing, using plants grown under controlled conditions as well as field cultivation at multiple sites. The spatial resolution of the study distinguished three root-associated compartments, the endosphere (root interior), rhizoplane (root surface), and rhizosphere (soil close to the root surface), each of which was found to harbor a distinct microbiome. Under controlled greenhouse conditions, microbiome composition varied with soil source and genotype. In field conditions, geographical location and cultivation practice, namely organic vs. conventional, were factors contributing to microbiome variation. Rice cultivation is a major source of global methane emissions, and methanogenic archaea could be detected in all spatial compartments of field-grown rice. The depth and scale of this study were used to build coabundance networks that revealed potential microbial consortia, some of which were involved in methane cycling. Dynamic changes observed during microbiome acquisition, as well as steady-state compositions of spatial compartments, support a multistep model for root microbiome assembly from soil wherein the rhizoplane plays a selective gating role. Similarities in the distribution of phyla in the root microbiomes of rice and other plants suggest that conclusions derived from this study might be generally applicable to land plants.
1,673 citations
TL;DR: It is shown that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair at CTCF sites, and it is found that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer.
Abstract: We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.
1,390 citations
TL;DR: The most comprehensive and most highly resolved economic input–output framework of the world economy together with a detailed database of global material flows are used to calculate the full material requirements of all countries covering a period of two decades and demonstrate that countries’ use of nondomestic resources is about threefold larger than the physical quantity of traded goods.
Abstract: Metrics on resource productivity currently used by governments suggest that some developed countries have increased the use of natural resources at a slower rate than economic growth (relative decoupling) or have even managed to use fewer resources over time (absolute decoupling). Using the material footprint (MF), a consumption-based indicator of resource use, we find the contrary: Achievements in decoupling in advanced economies are smaller than reported or even nonexistent. We present a time series analysis of the MF of 186 countries and identify material flows associated with global production and consumption networks in unprecedented specificity. By calculating raw material equivalents of international trade, we demonstrate that countries’ use of nondomestic resources is, on average, about threefold larger than the physical quantity of traded goods. As wealth grows, countries tend to reduce their domestic portion of materials extraction through international trade, whereas the overall mass of material consumption generally increases. With every 10% increase in gross domestic product, the average national MF increases by 6%. Our findings call into question the sole use of current resource productivity indicators in policy making and suggest the necessity of an additional focus on consumption-based accounting for natural resource use.
1,182 citations
TL;DR: In this article, the authors discuss the potential of black phosphorus (black P) as a 2D layered material for nanoelectronics and nanophotonics, and give their perspectives on future 2D and thin-film black P research directions.
Abstract: One hundred years after its first successful synthesis in the bulk form in 1914, black phosphorus (black P) was recently rediscovered from the perspective of a 2D layered material, attracting tremendous interest from condensed matter physicists, chemists, semiconductor device engineers, and material scientists. Similar to graphite and transition metal dichalcogenides (TMDs), black P has a layered structure but with a unique puckered single-layer geometry. Because the direct electronic band gap of thin film black P can be varied from 0.3 eV to around 2 eV, depending on its film thickness, and because of its high carrier mobility and anisotropic in-plane properties, black P is promising for novel applications in nanoelectronics and nanophotonics different from graphene and TMDs. Black P as a nanomaterial has already attracted much attention from researchers within the past year. Here, we offer our opinions on this emerging material with the goal of motivating and inspiring fellow researchers in the 2D materials community and the broad readership of PNAS to discuss and contribute to this exciting new field. We also give our perspectives on future 2D and thin film black P research directions, aiming to assist researchers coming from a variety of disciplines who are desirous of working in this exciting research field.
1,152 citations
TL;DR: This work has developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures, and can predict the protein fold down to the topology level following the CATH classification from a single CD spectrum.
Abstract: Circular dichroism (CD) spectroscopy is a widely used technique for the study of protein structure. Numerous algorithms have been developed for the estimation of the secondary structure composition from the CD spectra. These methods often fail to provide acceptable results on α/β-mixed or β-structure–rich proteins. The problem arises from the spectral diversity of β-structures, which has hitherto been considered as an intrinsic limitation of the technique. The predictions are less reliable for proteins of unusual β-structures such as membrane proteins, protein aggregates, and amyloid fibrils. Here, we show that the parallel/antiparallel orientation and the twisting of the β-sheets account for the observed spectral diversity. We have developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures. This method can reliably distinguish parallel and antiparallel β-sheets and accurately estimates the secondary structure for a broad range of proteins. Moreover, the secondary structure components applied by the method are characteristic to the protein fold, and thus the fold can be predicted to the level of topology in the CATH classification from a single CD spectrum. By constructing a web server, we offer a general tool for a quick and reliable structure analysis using conventional CD or synchrotron radiation CD (SRCD) spectroscopy for the protein science research community. The method is especially useful when X-ray or NMR techniques fail. Using BeStSel on data collected by SRCD spectroscopy, we investigated the structure of amyloid fibrils of various disease-related proteins and peptides.
1,137 citations
TL;DR: The first, to the authors' knowledge, single cell whole transcriptome analysis of human adult cortical samples is described, establishing an experimental and analytical framework with which the complexity of the human brain can be dissected on the single cell level.
Abstract: The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.
1,121 citations
TL;DR: A heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse- grained metal.
Abstract: Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems.
1,063 citations
TL;DR: It is shown that penta-graphene, composed of only carbon pentagons and resembling Cairo pentagonal tiling, is dynamically, thermally, and mechanically stable, and exhibits negative Poisson's ratio, a large band gap, and an ultrahigh mechanical strength.
Abstract: A 2D metastable carbon allotrope, penta-graphene, composed entirely of carbon pentagons and resembling the Cairo pentagonal tiling, is proposed. State-of-the-art theoretical calculations confirm that the new carbon polymorph is not only dynamically and mechanically stable, but also can withstand temperatures as high as 1000 K. Due to its unique atomic configuration, penta-graphene has an unusual negative Poisson’s ratio and ultrahigh ideal strength that can even outperform graphene. Furthermore, unlike graphene that needs to be functionalized for opening a band gap, penta-graphene possesses an intrinsic quasi-direct band gap as large as 3.25 eV, close to that of ZnO and GaN. Equally important, penta-graphene can be exfoliated from T12-carbon. When rolled up, it can form pentagon-based nanotubes which are semiconducting, regardless of their chirality. When stacked in different patterns, stable 3D twin structures of T12-carbon are generated with band gaps even larger than that of T12-carbon. The versatility of penta-graphene and its derivatives are expected to have broad applications in nanoelectronics and nanomechanics.
1,060 citations
TL;DR: A general strategy to produce numerous gRNAs from a single polycistronic gene via the endogenous tRNA-processing system is developed and shown to significantly increase CRISPR/Cas9 multiplex editing capability and efficiency in plants and is expected to have broad applications for small RNA expression and genome engineering.
Abstract: The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system is being harnessed as a powerful tool for genome engineering in basic research, molecular therapy, and crop improvement. This system uses a small guide RNA (gRNA) to direct Cas9 endonuclease to a specific DNA site; thus, its targeting capability is largely constrained by the gRNA-expressing device. In this study, we developed a general strategy to produce numerous gRNAs from a single polycistronic gene. The endogenous tRNA-processing system, which precisely cleaves both ends of the tRNA precursor, was engineered as a simple and robust platform to boost the targeting and multiplex editing capability of the CRISPR/Cas9 system. We demonstrated that synthetic genes with tandemly arrayed tRNA–gRNA architecture were efficiently and precisely processed into gRNAs with desired 5′ targeting sequences in vivo, which directed Cas9 to edit multiple chromosomal targets. Using this strategy, multiplex genome editing and chromosomal-fragment deletion were readily achieved in stable transgenic rice plants with a high efficiency (up to 100%). Because tRNA and its processing system are virtually conserved in all living organisms, this method could be broadly used to boost the targeting capability and editing efficiency of CRISPR/Cas9 toolkits.
TL;DR: This paper found that precipitation deficits in California were more than twice as likely to yield drought years if they occurred when conditions were warm and that anthropogenic warming is increasing the probability of co-occurring warm-dry conditions like those that have created the acute human and ecosystem impacts associated with the 2012-2014 drought in California.
Abstract: California is currently in the midst of a record-setting drought. The drought began in 2012 and now includes the lowest calendar-year and 12-mo precipitation, the highest annual temperature, and the most extreme drought indicators on record. The extremely warm and dry conditions have led to acute water shortages, groundwater overdraft, critically low streamflow, and enhanced wildfire risk. Analyzing historical climate observations from California, we find that precipitation deficits in California were more than twice as likely to yield drought years if they occurred when conditions were warm. We find that although there has not been a substantial change in the probability of either negative or moderately negative precipitation anomalies in recent decades, the occurrence of drought years has been greater in the past two decades than in the preceding century. In addition, the probability that precipitation deficits co-occur with warm conditions and the probability that precipitation deficits produce drought have both increased. Climate model experiments with and without anthropogenic forcings reveal that human activities have increased the probability that dry precipitation years are also warm. Further, a large ensemble of climate model realizations reveals that additional global warming over the next few decades is very likely to create ∼100% probability that any annual-scale dry period is also extremely warm. We therefore conclude that anthropogenic warming is increasing the probability of co-occurring warm–dry conditions like those that have created the acute human and ecosystem impacts associated with the “exceptional” 2012–2014 drought in California.
TL;DR: It is shown that the recent decrease in Syrian precipitation is a combination of natural variability and a long-term drying trend, and the unusual severity of the observed drought is here shown to be highly unlikely without this trend.
Abstract: Before the Syrian uprising that began in 2011, the greater Fertile Crescent experienced the most severe drought in the instrumental record. For Syria, a country marked by poor governance and unsustainable agricultural and environmental policies, the drought had a catalytic effect, contributing to political unrest. We show that the recent decrease in Syrian precipitation is a combination of natural variability and a long-term drying trend, and the unusual severity of the observed drought is here shown to be highly unlikely without this trend. Precipitation changes in Syria are linked to rising mean sea-level pressure in the Eastern Mediterranean, which also shows a long-term trend. There has been also a long-term warming trend in the Eastern Mediterranean, adding to the drawdown of soil moisture. No natural cause is apparent for these trends, whereas the observed drying and warming are consistent with model studies of the response to increases in greenhouse gases. Furthermore, model studies show an increasingly drier and hotter future mean climate for the Eastern Mediterranean. Analyses of observations and model simulations indicate that a drought of the severity and duration of the recent Syrian drought, which is implicated in the current conflict, has become more than twice as likely as a consequence of human interference in the climate system.
TL;DR: It is demonstrated that an N-terminal, arginine/glycine rich, intrinsically disordered protein (IDP) domain of LAF-1 is necessary and sufficient for both phase separation and RNA–protein interactions, and insight is provided into the mechanism by which IDP-driven molecular interactions give rise to liquid phase organelles with tunable properties.
Abstract: P granules and other RNA/protein bodies are membrane-less organelles that may assemble by intracellular phase separation, similar to the condensation of water vapor into droplets. However, the molecular driving forces and the nature of the condensed phases remain poorly understood. Here, we show that the Caenorhabditis elegans protein LAF-1, a DDX3 RNA helicase found in P granules, phase separates into P granule-like droplets in vitro. We adapt a microrheology technique to precisely measure the viscoelasticity of micrometer-sized LAF-1 droplets, revealing purely viscous properties highly tunable by salt and RNA concentration. RNA decreases viscosity and increases molecular dynamics within the droplet. Single molecule FRET assays suggest that this RNA fluidization results from highly dynamic RNA–protein interactions that emerge close to the droplet phase boundary. We demonstrate than an N-terminal, arginine/glycine rich, intrinsically disordered protein (IDP) domain of LAF-1 is necessary and sufficient for both phase separation and RNA–protein interactions. In vivo, RNAi knockdown of LAF-1 results in the dissolution of P granules in the early embryo, with an apparent submicromolar phase boundary comparable to that measured in vitro. Together, these findings demonstrate that LAF-1 is important for promoting P granule assembly and provide insight into the mechanism by which IDP-driven molecular interactions give rise to liquid phase organelles with tunable properties.
University of Melbourne1, University of Oxford2, Cornell University3, United States Army Medical Research Institute of Infectious Diseases4, Cardiff University5, University Health System6, Erasmus University Medical Center7, Pasteur Institute8, University of California, San Francisco9, University of Queensland10, University of Amsterdam11, Airlangga University12, Mahosot Hospital13, Wellcome Trust14, University of London15
TL;DR: The DNA sequence of K. pneumoniae isolates from around the world is determined and it is shown that there is a wide spectrum of diversity, including variation within shared sequences and gain and loss of whole genes, and there is an unrecognized association between the possession of specific gene profiles associated with virulence and antibiotic resistance.
Abstract: Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.
University of Colorado Boulder1, University of Notre Dame2, Commonwealth Scientific and Industrial Research Organisation3, University of Minnesota4, Queensland University of Technology5, Martin Luther University of Halle-Wittenberg6, Iowa State University7, University of Nebraska–Lincoln8, University of Kentucky9, University of California, Berkeley10, Swiss Federal Institute for Forest, Snow and Landscape Research11, Lancaster University12
TL;DR: The results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.
Abstract: Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.
TL;DR: A highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR).
Abstract: Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an ∼17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into ∼99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from nonhomologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.
TL;DR: A conceptual model that couples the stochastic/deterministic balance to primary and secondary ecological succession, thereby integrating previously isolated conceptual domains and providing a priori hypotheses for future experiments is presented, facilitating a systematic approach to understand assembly and succession in microbial communities across ecosystems.
Abstract: Ecological succession and the balance between stochastic and deterministic processes are two major themes within microbial ecology, but these conceptual domains have mostly developed independent of each other. Here we provide a framework that integrates shifts in community assembly processes with microbial primary succession to better understand mechanisms governing the stochastic/deterministic balance. Synthesizing previous work, we devised a conceptual model that links ecosystem development to alternative hypotheses related to shifts in ecological assembly processes. Conceptual model hypotheses were tested by coupling spatiotemporal data on soil bacterial communities with environmental conditions in a salt marsh chronosequence spanning 105 years of succession. Analyses within successional stages showed community composition to be initially governed by stochasticity, but as succession proceeded, there was a progressive increase in deterministic selection correlated with increasing sodium concentration. Analyses of community turnover among successional stages—which provide a larger spatiotemporal scale relative to within stage analyses—revealed that changes in the concentration of soil organic matter were the main predictor of the type and relative influence of determinism. Taken together, these results suggest scale-dependency in the mechanisms underlying selection. To better understand mechanisms governing these patterns, we developed an ecological simulation model that revealed how changes in selective environments cause shifts in the stochastic/deterministic balance. Finally, we propose an extended—and experimentally testable—conceptual model integrating ecological assembly processes with primary and secondary succession. This framework provides a priori hypotheses for future experiments, thereby facilitating a systematic approach to understand assembly and succession in microbial communities across ecosystems.
TL;DR: It is found that the use of portable light-emitting devices immediately before bedtime has biological effects that may perpetuate sleep deficiency and disrupt circadian rhythms, both of which can have adverse impacts on performance, health, and safety.
Abstract: In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength–enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced nextmorning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.
TL;DR: It is suggested that pregnancy outcomes might be predicted by features of the microbiota early in gestation, as well as the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.
Abstract: Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.
TL;DR: A comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.
Abstract: Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.
TL;DR: Here, it is found that for processes which are approximately cyclic, the second law for microscopic systems takes on a different form compared to the macroscopic scale, imposing not just one constraint on state transformations, but an entire family of constraints.
Abstract: The second law of thermodynamics places constraints on state transformations. It applies to systems composed of many particles, however, we are seeing that one can formulate laws of thermodynamics when only a small number of particles are interacting with a heat bath. Is there a second law of thermodynamics in this regime? Here, we find that for processes which are approximately cyclic, the second law for microscopic systems takes on a different form compared to the macroscopic scale, imposing not just one constraint on state transformations, but an entire family of constraints. We find a family of free energies which generalize the traditional one, and show that they can never increase. The ordinary second law relates to one of these, with the remainder imposing additional constraints on thermodynamic transitions. We find three regimes which determine which family of second laws govern state transitions, depending on how cyclic the process is. In one regime one can cause an apparent violation of the usual second law, through a process of embezzling work from a large system which remains arbitrarily close to its original state. These second laws are relevant for small systems, and also apply to individual macroscopic systems interacting via long-range interactions. By making precise the definition of thermal operations, the laws of thermodynamics are unified in this framework, with the first law defining the class of operations, the zeroth law emerging as an equivalence relation between thermal states, and the remaining laws being monotonicity of our generalized free energies.
TL;DR: Some of the driving theoretical ideas and first experimental realizations of hybrid quantum systems and the opportunities and challenges they present are reviewed and offers a glance at the near- and long-term perspectives of this fascinating and rapidly expanding field.
Abstract: An extensively pursued current direction of research in physics aims at the development of practical technologies that exploit the effects of quantum mechanics. As part of this ongoing effort, devices for quantum information processing, secure communication, and high-precision sensing are being implemented with diverse systems, ranging from photons, atoms, and spins to mesoscopic superconducting and nanomechanical structures. Their physical properties make some of these systems better suited than others for specific tasks; thus, photons are well suited for transmitting quantum information, weakly interacting spins can serve as long-lived quantum memories, and superconducting elements can rapidly process information encoded in their quantum states. A central goal of the envisaged quantum technologies is to develop devices that can simultaneously perform several of these tasks, namely, reliably store, process, and transmit quantum information. Hybrid quantum systems composed of different physical components with complementary functionalities may provide precisely such multitasking capabilities. This article reviews some of the driving theoretical ideas and first experimental realizations of hybrid quantum systems and the opportunities and challenges they present and offers a glance at the near- and long-term perspectives of this fascinating and rapidly expanding field.
TL;DR: It is shown that computers’ judgments of people’s personalities based on their digital footprints are more accurate and valid than judgments made by their close others or acquaintances, and that computer personality judgments have higher external validity when predicting life outcomes such as substance use, political attitudes, and physical health.
Abstract: Judging others’ personalities is an essential skill in successful social living, as personality is a key driver behind people’s interactions, behaviors, and emotions. Although accurate personality judgments stem from social-cognitive skills, developments in machine learning show that computer models can also make valid judgments. This study compares the accuracy of human and computer-based personality judgments, using a sample of 86,220 volunteers who completed a 100-item personality questionnaire. We show that (i) computer predictions based on a generic digital footprint (Facebook Likes) are more accurate (r = 0.56) than those made by the participants’ Facebook friends using a personality questionnaire (r = 0.49); (ii) computer models show higher interjudge agreement; and (iii) computer personality judgments have higher external validity when predicting life outcomes such as substance use, political attitudes, and physical health; for some outcomes, they even outperform the self-rated personality scores. Computers outpacing humans in personality judgment presents significant opportunities and challenges in the areas of psychological assessment, marketing, and privacy.
Stanford University1, University of Washington2, University of Minnesota3, Oregon State University4, Royal Swedish Academy of Sciences5, University of East Anglia6, Stockholm University7, World Wide Fund for Nature8, The Nature Conservancy9, Philippine Institute for Development Studies10, Chinese Academy of Sciences11, Council for Scientific and Industrial Research12, University of Vermont13, University of Cambridge14
TL;DR: Why ecosystem service information has yet to fundamentally change decision-making is explored and a path forward is suggested that emphasizes developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being.
Abstract: The central challenge of the 21st century is to develop economic, social, and governance systems capable of ending poverty and achieving sustainable levels of population and consumption while securing the life-support systems underpinning current and future human well-being. Essential to meeting this challenge is the incorporation of natural capital and the ecosystem services it provides into decision-making. We explore progress and crucial gaps at this frontier, reflecting upon the 10 y since the Millennium Ecosystem Assessment. We focus on three key dimensions of progress and ongoing challenges: raising awareness of the interdependence of ecosystems and human well-being, advancing the fundamental interdisciplinary science of ecosystem services, and implementing this science in decisions to restore natural capital and use it sustainably. Awareness of human dependence on nature is at an all-time high, the science of ecosystem services is rapidly advancing, and talk of natural capital is now common from governments to corporate boardrooms. However, successful implementation is still in early stages. We explore why ecosystem service information has yet to fundamentally change decision-making and suggest a path forward that emphasizes: (i) developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being; (ii) working closely with leaders in government, business, and civil society to develop the knowledge, tools, and practices necessary to integrate natural capital and ecosystem services into everyday decision-making; and (iii) reforming institutions to change policy and practices to better align private short-term goals with societal long-term goals.
University of Illinois at Urbana–Champaign1, United States Department of Agriculture2, University of California, Los Angeles3, Centre national de la recherche scientifique4, University of Oregon5, Washington University in St. Louis6, Max Planck Society7, VU University Amsterdam8, Cornell University9, University of Cambridge10, Arizona State University11, Louisiana State University12, Lawrence Berkeley National Laboratory13, University of California, Berkeley14, Rothamsted Research15, Georgia Institute of Technology16, ExxonMobil17, Iowa State University18, Australian National University19, University of Düsseldorf20, Texas A&M University21
TL;DR: This work explores an array of prospective redesigns of plant systems at various scales aimed at increasing crop yields through improved photosynthetic efficiency and performance, and suggests some proposed redesigns are certain to face obstacles that will require alternate routes.
Abstract: The world’s crop productivity is stagnating whereas population growth, rising affluence, and mandates for biofuels put increasing demands on agriculture. Meanwhile, demand for increasing cropland competes with equally crucial global sustainability and environmental protection needs. Addressing this looming agricultural crisis will be one of our greatest scientific challenges in the coming decades, and success will require substantial improvements at many levels. We assert that increasing the efficiency and productivity of photosynthesis in crop plants will be essential if this grand challenge is to be met. Here, we explore an array of prospective redesigns of plant systems at various scales, all aimed at increasing crop yields through improved photosynthetic efficiency and performance. Prospects range from straightforward alterations, already supported by preliminary evidence of feasibility, to substantial redesigns that are currently only conceptual, but that may be enabled by new developments in synthetic biology. Although some proposed redesigns are certain to face obstacles that will require alternate routes, the efforts should lead to new discoveries and technical advances with important impacts on the global problem of crop productivity and bioenergy production.
TL;DR: This work presents an experimental and theoretical study of an active metamaterial—composed of coupled gyroscopes on a lattice—that breaks time-reversal symmetry and presents a mathematical model that explains how the edge mode chirality can be switched via controlled distortions of the underlying lattice.
Abstract: Topological mechanical metamaterials are artificial structures whose unusual properties are protected very much like their electronic and optical counterparts. Here, we present an experimental and theoretical study of an active metamaterial--composed of coupled gyroscopes on a lattice--that breaks time-reversal symmetry. The vibrational spectrum displays a sonic gap populated by topologically protected edge modes that propagate in only one direction and are unaffected by disorder. We present a mathematical model that explains how the edge mode chirality can be switched via controlled distortions of the underlying lattice. This effect allows the direction of the edge current to be determined on demand. We demonstrate this functionality in experiment and envision applications of these edge modes to the design of one-way acoustic waveguides.
TL;DR: Comparing the results from conjoint and vignette experiments on which attributes of hypothetical immigrants generate support for naturalization with the outcomes of closely corresponding referendums in Switzerland, it is found that the effects estimated from the surveys match the effects of the same attributes in the behavioral benchmark remarkably well.
Abstract: Survey experiments, like vignette and conjoint analyses, are widely used in the social sciences to elicit stated preferences and study how humans make multidimensional choices. However, there is a paucity of research on the external validity of these methods that examines whether the determinants that explain hypothetical choices made by survey respondents match the determinants that explain what subjects actually do when making similar choices in real-world situations. This study compares results from conjoint and vignette analyses on which immigrant attributes generate support for naturalization with closely corresponding behavioral data from a natural experiment in Switzerland, where some municipalities used referendums to decide on the citizenship applications of foreign residents. Using a representative sample from the same population and the official descriptions of applicant characteristics that voters received before each referendum as a behavioral benchmark, we find that the effects of the applicant attributes estimated from the survey experiments perform remarkably well in recovering the effects of the same attributes in the behavioral benchmark. We also find important differences in the relative performances of the different designs. Overall, the paired conjoint design, where respondents evaluate two immigrants side by side, comes closest to the behavioral benchmark; on average, its estimates are within 2% percentage points of the effects in the behavioral benchmark.
TL;DR: The loss of Australian land mammals is most likely due primarily to predation by introduced species, particularly the feral cat, Felis catus, and European red fox, Vulpes vulpes, and changed fire regimes.
Abstract: The highly distinctive and mostly endemic Australian land mammal fauna has suffered an extraordinary rate of extinction (>10% of the 273 endemic terrestrial species) over the last ∼200 y: in comparison, only one native land mammal from continental North America became extinct since European settlement. A further 21% of Australian endemic land mammal species are now assessed to be threatened, indicating that the rate of loss (of one to two extinctions per decade) is likely to continue. Australia’s marine mammals have fared better overall, but status assessment for them is seriously impeded by lack of information. Much of the loss of Australian land mammal fauna (particularly in the vast deserts and tropical savannas) has been in areas that are remote from human population centers and recognized as relatively unmodified at global scale. In contrast to general patterns of extinction on other continents where the main cause is habitat loss, hunting, and impacts of human development, particularly in areas of high and increasing human population pressures, the loss of Australian land mammals is most likely due primarily to predation by introduced species, particularly the feral cat, Felis catus, and European red fox, Vulpes vulpes, and changed fire regimes.
TL;DR: These complex relationships between phenotypic differences and the dynamics of competing species argue against the simple use of single functional traits to infer community assembly processes but lay the groundwork for a theoretically justified trait-based community ecology.
Abstract: Understanding the processes maintaining species diversity is a central problem in ecology, with implications for the conservation and management of ecosystems. Although biologists often assume that trait differences between competitors promote diversity, empirical evidence connecting functional traits to the niche differences that stabilize species coexistence is rare. Obtaining such evidence is critical because traits also underlie the average fitness differences driving competitive exclusion, and this complicates efforts to infer community dynamics from phenotypic patterns. We coupled field-parameterized mathematical models of competition between 102 pairs of annual plants with detailed sampling of leaf, seed, root, and whole-plant functional traits to relate phenotypic differences to stabilizing niche and average fitness differences. Single functional traits were often well correlated with average fitness differences between species, indicating that competitive dominance was associated with late phenology, deep rooting, and several other traits. In contrast, single functional traits were poorly correlated with the stabilizing niche differences that promote coexistence. Niche differences could only be described by combinations of traits, corresponding to differentiation between species in multiple ecological dimensions. In addition, several traits were associated with both fitness differences and stabilizing niche differences. These complex relationships between phenotypic differences and the dynamics of competing species argue against the simple use of single functional traits to infer community assembly processes but lay the groundwork for a theoretically justified trait-based community ecology.