Showing papers by "Colorado State University published in 2013"
TL;DR: It is proposed that labile plant constituents are the dominant source of microbial products, relative to input rates, because they are utilized more efficiently by microbes, and become the main precursors of stable SOM by promoting aggregation and through strong chemical bonding to the mineral soil matrix.
Abstract: The decomposition and transformation of above- and below-ground plant detritus (litter) is the main process by which soil organic matter (SOM) is formed. Yet, research on litter decay and SOM formation has been largely uncoupled, failing to provide an effective nexus between these two fundamental processes for carbon (C) and nitrogen (N) cycling and storage. We present the current understanding of the importance of microbial substrate use efficiency and C and N allocation in controlling the proportion of plant-derived C and N that is incorporated into SOM, and of soil matrix interactions in controlling SOM stabilization. We synthesize this understanding into the Microbial Efficiency-Matrix Stabilization (MEMS) framework. This framework leads to the hypothesis that labile plant constituents are the dominant source of microbial products, relative to input rates, because they are utilized more efficiently by microbes. These microbial products of decomposition would thus become the main precursors of stable SOM by promoting aggregation and through strong chemical bonding to the mineral soil matrix.
1,851 citations
TL;DR: The collective vision of the future of extracellular enzyme research is offered: one that will depend on imaginative thinking as well as technological advances, and be built upon synergies between diverse disciplines.
Abstract: This review focuses on some important and challenging aspects of soil extracellular enzyme research. We report on recent discoveries, identify key research needs and highlight the many opportunities offered by interactions with other microbial enzymologists. The biggest challenges are to understand how the chemical, physical and biological properties of soil affect enzyme production, diffusion, substrate turnover and the proportion of the product that is made available to the producer cells. Thus, the factors that regulate the synthesis and secretion of extracellular enzymes and their distribution after they are externalized are important topics, not only for soil enzymologists, but also in the broader context of microbial ecology. In addition, there are many uncertainties about the ways in which microbes and their extracellular enzymes overcome the generally destructive, inhibitory and competitive properties of the soil matrix, and the various strategies they adopt for effective substrate detection and utilization. The complexity of extracellular enzyme activities in depolymerising macromolecular organics is exemplified by lignocellulose degradation and how the many enzymes involved respond to structural diversity and changing nutrient availabilities. The impacts of climate change on microbes and their extracellular enzymes, although of profound importance, are not well understood but we suggest how they may be predicted, assessed and managed. We describe recent advances that allow for the manipulation of extracellular enzyme activities to facilitate bioremediation, carbon sequestration and plant growth promotion. We also contribute to the ongoing debate as to how to assay enzyme activities in soil and what the measurements tell us, in the context of both traditional methods and the newer techniques that are being developed and adopted. Finally, we offer our collective vision of the future of extracellular enzyme research: one that will depend on imaginative thinking as well as technological advances, and be built upon synergies between diverse disciplines.
1,475 citations
TL;DR: In this article, a definition for the term ''halogen bond'' is proposed, which designates a specific subset of the inter-and intramolecular interactions involving a halogen atom in a molecular entity.
Abstract: This recommendation proposes a definition for the term ``halogen bond'', which designates a specific subset of the inter- and intramolecular interactions involving a halogen atom in a molecular entity.
1,386 citations
University of Pennsylvania1, Colorado State University2, Mayo Clinic3, Harvard University4, National Institutes of Health5, King's College London6, University of Freiburg7, Washington University in St. Louis8, Stanford University9, University of Miami10, Boston Biomedical Research Institute11, University of California, Irvine12
TL;DR: Dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease and related proteins with PrLDs should be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
Abstract: Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
1,209 citations
University of Sydney1, University of Western Australia2, Commonwealth Scientific and Industrial Research Organisation3, James Cook University4, Rothamsted Research5, Argonne National Laboratory6, Ohio State University7, Cornell University8, Colorado State University9, Landcare Research10, University of Natural Resources and Life Sciences, Vienna11
TL;DR: In this article, a review highlights knowledge of the amount of carbon stored in soils globally, and the potential for carbon sequestration in soil, and discusses successful methods and models used to determine and estimate carbon pools and fluxes.
1,128 citations
TL;DR: Xylem pit anatomy that makes xylem less “leaky” and prone to cavitation warrants further exploration holding promise that such traits may improve plant productivity in water-limited environments without negatively impacting yield under adequate water conditions.
Abstract: Geneticists and breeders are positioned to breed plants with root traits that improve productivity under drought. However, a better understanding of root functional traits and how traits are related to whole plant strategies to increase crop productivity under different drought conditions is needed. Root traits associated with maintaining plant productivity under drought include small fine root diameters, long specific root length, and considerable root length density, especially at depths in soil with available water. In environments with late season water deficits, small xylem diameters in targeted seminal roots save soil water deep in the soil profile for use during crop maturation and result in improved yields. Capacity for deep root growth and large xylem diameters in deep roots may also improve root acquisition of water when ample water at depth is available. Xylem pit anatomy that makes xylem less "leaky" and prone to cavitation warrants further exploration holding promise that such traits may improve plant productivity in water-limited environments without negatively impacting yield under adequate water conditions. Rapid resumption of root growth following soil rewetting may improve plant productivity under episodic drought. Genetic control of many of these traits through breeding appears feasible. Several recent reviews have covered methods for screening root traits but an appreciation for the complexity of root systems (e.g., functional differences between fine and coarse roots) needs to be paired with these methods to successfully identify relevant traits for crop improvement. Screening of root traits at early stages in plant development can proxy traits at mature stages but verification is needed on a case by case basis that traits are linked to increased crop productivity under drought. Examples in lesquerella (Physaria) and rice (Oryza) show approaches to phenotyping of root traits and current understanding of root trait genetics for breeding.
971 citations
Indiana University1, Buck Institute for Research on Aging2, University of California, San Francisco3, University of California, Santa Cruz4, Colorado State University5, University of Colorado Denver6, University of California, Berkeley7, Icahn School of Medicine at Mount Sinai8, European Bioinformatics Institute9, University of Bologna10, University of Missouri11, University of Bristol12, University of Helsinki13, University College London14, Centre for Development of Advanced Computing15, Purdue University16, Baylor College of Medicine17, Royal Holloway, University of London18, Technische Universität München19, University of Turku20, Queen's University21, University UCINF22, Max Planck Society23, Imperial College London24, Wageningen University and Research Centre25, Nestlé26, Fudan University27, University of Padua28, Temple University29, University of Geneva30, Swiss Institute of Bioinformatics31, Hebrew University of Jerusalem32, Miami University33
TL;DR: Today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets, and there is considerable need for improvement of currently available tools.
Abstract: Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.
859 citations
Leibniz Association1, University of Potsdam2, Technische Universität München3, Colorado State University4, University of Oxford5, Wildlife Conservation Society6, University of California, Davis7, Indonesian Institute of Sciences8, Mulawarman University9, Universiti Malaysia Sabah10, Kyoto University11, International Union for Conservation of Nature and Natural Resources12, Mississippi State University13
TL;DR: It is concluded that a substantial improvement in the quality of model predictions can be achieved if uneven sampling effort is taken into account, thereby improving the efficacy of species conservation planning.
Abstract: Aim
Advancement in ecological methods predicting species distributions is a crucial precondition for deriving sound management actions. Maximum entropy (MaxEnt) models are a popular tool to predict species distributions, as they are considered able to cope well with sparse, irregularly sampled data and minor location errors. Although a fundamental assumption of MaxEnt is that the entire area of interest has been systematically sampled, in practice, MaxEnt models are usually built from occurrence records that are spatially biased towards better-surveyed areas. Two common, yet not compared, strategies to cope with uneven sampling effort are spatial filtering of occurrence data and background manipulation using environmental data with the same spatial bias as occurrence data. We tested these strategies using simulated data and a recently collated dataset on Malay civet Viverra tangalunga in Borneo.
Location
Borneo, Southeast Asia.
Methods
We collated 504 occurrence records of Malay civets from Borneo of which 291 records were from 2001 to 2011 and used them in the MaxEnt analysis (baseline scenario) together with 25 environmental input variables. We simulated datasets for two virtual species (similar to a range-restricted highland and a lowland species) using the same number of records for model building. As occurrence records were biased towards north-eastern Borneo, we investigated the efficacy of spatial filtering versus background manipulation to reduce overprediction or underprediction in specific areas.
Results
Spatial filtering minimized omission errors (false negatives) and commission errors (false positives). We recommend that when sample size is insufficient to allow spatial filtering, manipulation of the background dataset is preferable to not correcting for sampling bias, although predictions were comparatively weak and commission errors increased.
Main Conclusions
We conclude that a substantial improvement in the quality of model predictions can be achieved if uneven sampling effort is taken into account, thereby improving the efficacy of species conservation planning.
822 citations
TL;DR: A sensitivity analysis on a global model is performed to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes and suggests that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.
Abstract: The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates. The impact of aerosol changes on cloud albedo (called the aerosol first indirect forcing) 1 is estimated 2 to exert a global mean radiative forcing of climate over the industrial period between 20.4 W m 22 and 21.8 W m 22 . Other aerosol–cloud interaction effects, involving rapid adjustments, may be of comparable magnitude 3 but their radiative effects are even less well understood on a global scale 3,4 . The uncertainty in the aerosol forcing is much larger than the uncertainty in the well-constrained positive forcing of 1.7 6 0.2 W m 22 that is due to
818 citations
TL;DR: The results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles.
720 citations
Pablo de Olavide University1, King Juan Carlos University2, Northern Arizona University3, Colorado State University4, University of Córdoba (Spain)5, Instituto Potosino de Investigación Científica y Tecnológica6, University of La Serena7, University of Jaén8, University of Sfax9, State University of Feira de Santana10, University of New South Wales11, Universidad Técnica Particular de Loja12, National University of San Juan13, University of the Bío Bío14, Central University of Venezuela15, National University of La Pampa16, Virginia Tech College of Natural Resources and Environment17, Northeast Normal University18, Ohio State University19, Université du Québec à Montréal20, International Potato Center21, University of New England (Australia)22, Universidad Centroccidental Lisandro Alvarado23, Agricultural Research Organization, Volcani Center24, Office of Environment and Heritage25
TL;DR: Any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P, suggesting the provision of key services provided by these ecosystems could be negatively affected.
Abstract: The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems. It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes. Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability. The increase in aridity predicted for the twenty-first century in many drylands worldwide may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients. Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition. Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.
TL;DR: In this article, the Allostatic Load model is used as an organizing framework for reviewing the vast literature that has considered health outcomes that are associated with exposure to psychosocial stressors at work.
TL;DR: Widespread changes in AS in response to developmental cues and stresses suggest a role for regulated splicing in plant development and stress responses, and new tools based on recent technological advances are allowing genome-wide analysis of RNA elements in transcripts and of chromatin modifications that regulate AS.
Abstract: Alternative splicing (AS) of precursor mRNAs (pre-mRNAs) from multiexon genes allows organisms to increase their coding potential and regulate gene expression through multiple mechanisms. Recent transcriptome-wide analysis of AS using RNA sequencing has revealed that AS is highly pervasive in plants. Pre-mRNAs from over 60% of intron-containing genes undergo AS to produce a vast repertoire of mRNA isoforms. The functions of most splice variants are unknown. However, emerging evidence indicates that splice variants increase the functional diversity of proteins. Furthermore, AS is coupled to transcript stability and translation through nonsense-mediated decay and microRNA-mediated gene regulation. Widespread changes in AS in response to developmental cues and stresses suggest a role for regulated splicing in plant development and stress responses. Here, we review recent progress in uncovering the extent and complexity of the AS landscape in plants, its regulation, and the roles of AS in gene regulation. The prevalence of AS in plants has raised many new questions that require additional studies. New tools based on recent technological advances are allowing genome-wide analysis of RNA elements in transcripts and of chromatin modifications that regulate AS. Application of these tools in plants will provide significant new insights into AS regulation and crosstalk between AS and other layers of gene regulation.
TL;DR: The concept for this analysis is to a large degree based on earlier BABAR work and we acknowledge the guidance provided by M. Mazur as discussed by the authors, who consulted with theorists A. Datta, S. Westhoff,S. Fajfer, J. Kamenik, and I. Nisandzic on the calculations of the charged Higgs contributions to the decay rates.
Abstract: The concept for this analysis is to a large degree based on earlier BABAR work and we acknowledge the guidance provided by M. Mazur. The authors consulted with theorists A. Datta, S. Westhoff, S. Fajfer, J. Kamenik, and I. Nisandzic on the calculations of the charged Higgs contributions to the decay rates. We are grateful for the extraordinary contributions of our PEP-II colleagues in achieving the excellent luminosity and machine conditions that have made this work possible. The success of this project also relied critically on the expertise and dedication of the computing organizations that support BABAR. The collaborating institutions wish to thank SLAC for its support and the kind hospitality extended to them. This work is supported by the U.S. Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat a l'Energie Atomique and Institut National de Physique Nucleaire et de Physique des Particules (France), the Bundesministerium fur Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Economia y Competitividad (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A. P. Sloan Foundation (USA).
TL;DR: In this article, the authors examined over 20 years of research on environmental supply chain practices using a meta-analysis to determine whether the overall effect of these specific practices on firm performance is, in fact, positive.
Abstract: Studies linking environmental sustainability to firm performance have been increasing as more companies are contemplating the implementation of sustainable practices internally and in coordination with other firms along their supply chains. However, findings from these studies have found positive and negative associations, leaving practitioners perplexed as to what actions would be beneficial to pursue. With hypotheses grounded in the natural resource–based view of the firm, the current study examines over 20 years of research on environmental supply chain practices using a meta-analysis to determine whether the overall effect of these specific practices on firm performance is, in fact, positive. The results show that the link between environmental supply chain practices and market-based, operational-based and accounting-based forms of firm performance is positive and significant, providing support for the business case that sustainable supply chain management results in increased firm performance. Different operationalizations of supply chain practices — upstream, design, production and downstream — along with industry, sample region, firm size and time are examined as moderators of this relationship with nuanced results that help to extend the discipline's understanding of the relationship between environmentally sustainable supply chain management and firm performance.
Colorado State University1, National Institutes of Health2, United States Geological Survey3, Centers for Disease Control and Prevention4, University of Florida5, Emory University6, University of Winnipeg7, Zoological Society of London8, Veterinary Laboratories Agency9, Global Alliance for Rabies Control10, University of Cambridge11
TL;DR: The results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents.
Abstract: Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.
TL;DR: Stool profiling was used to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to identify how microbial functions may influence CRC development.
Abstract: In this study we used stool profiling to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to identify how microbial functions may influence CRC development. Stool samples were collected from healthy adults (n = 10) and colorectal cancer patients (n = 11) prior to colon resection surgery at the University of Colorado Health-Poudre Valley Hospital in Fort Collins, CO. The V4 region of the 16s rRNA gene was pyrosequenced and both short chain fatty acids and global stool metabolites were extracted and analyzed utilizing Gas Chromatography-Mass Spectrometry (GC-MS). There were no significant differences in the overall microbial community structure associated with the disease state, but several bacterial genera, particularly butyrate-producing species, were under-represented in the CRC samples, while a mucin-degrading species, Akkermansia muciniphila, was about 4-fold higher in CRC (p<0.01). Proportionately higher amounts of butyrate were seen in stool of healthy individuals while relative concentrations of acetate were higher in stools of CRC patients. GC-MS profiling revealed higher concentrations of amino acids in stool samples from CRC patients and higher poly and monounsaturated fatty acids and ursodeoxycholic acid, a conjugated bile acid in stool samples from healthy adults (p<0.01). Correlative analysis between the combined datasets revealed some potential relationships between stool metabolites and certain bacterial species. These associations could provide insight into microbial functions occurring in a cancer environment and will help direct future mechanistic studies. Using integrated “omics” approaches may prove a useful tool in identifying functional groups of gastrointestinal bacteria and their associated metabolites as novel therapeutic and chemopreventive targets.
TL;DR: This study presents the first direct cloud and precipitation measurements showing that Saharan and Asian dust and biological aerosols probably serve as IN and play an important role in orographic precipitation processes over the western United States.
Abstract: Winter storms in California’s Sierra Nevada increase seasonal snowpack and provide critical water resources and hydropower for the state. Thus, the mechanisms influencing precipitation in this region have been the subject of research for decades. Previous studies suggest Asian dust enhances cloud ice and precipitation, whereas few studies consider biological aerosols as an important global source of ice nuclei (IN). Here, we show that dust and biological aerosols transported from as far as the Sahara were present in glaciated high-altitude clouds coincident with elevated IN concentrations and ice-induced precipitation. This study presents the first direct cloud and precipitation measurements showing that Saharan and Asian dust and biological aerosols probably serve as IN and play an important role in orographic precipitation processes over the western United States.
TL;DR: The results suggest that the root exudation process of phytochemicals follows a developmental pattern that is genetically programmed.
Abstract: Plant roots constantly secrete compounds into the soil to interact with neighboring organisms presumably to gain certain functional advantages at different stages of development. Accordingly, it has been hypothesized that the phytochemical composition present in the root exudates changes over the course of the lifespan of a plant. Here, root exudates of in vitro grown Arabidopsis plants were collected at different developmental stages and analyzed using GC-MS. Principle component analysis revealed that the composition of root exudates varied at each developmental stage. Cumulative secretion levels of sugars and sugar alcohols were higher in early time points and decreased through development. In contrast, the cumulative secretion levels of amino acids and phenolics increased over time. The expression in roots of genes involved in biosynthesis and transportation of compounds represented in the root exudates were consistent with patterns of root exudation. Correlation analyses were performed of the in vitro root exudation patterns with the functional capacity of the rhizosphere microbiome to metabolize these compounds at different developmental stages of Arabidopsis grown in natural soils. Pyrosequencing of rhizosphere mRNA revealed strong correlations (p<0.05) between microbial functional genes involved in the metabolism of carbohydrates, amino acids and secondary metabolites with the corresponding compounds released by the roots at particular stages of plant development. In summary, our results suggest that the root exudation process of phytochemicals follows a developmental pattern that is genetically programmed.
TL;DR: The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound.
Abstract: New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.
North Carolina State University1, National Oceanic and Atmospheric Administration2, University at Albany, SUNY3, Northern Illinois University4, University of South Carolina5, Colorado State University6, Massachusetts Institute of Technology7, National Center for Atmospheric Research8, Geophysical Fluid Dynamics Laboratory9, Florida State University10, University of California, Berkeley11, Desert Research Institute12, Rutgers University13, Purdue University14, Lawrence Berkeley National Laboratory15, University of Colorado Boulder16, University of Illinois at Urbana–Champaign17
TL;DR: The state of knowledge regarding trends and an understanding of their causes for a specific subset of extreme weather and climate types is presented in this paper for severe convective storms (tornadoes, hailstorms, and severe thunderstorms).
Abstract: The state of knowledge regarding trends and an understanding of their causes is presented for a specific subset of extreme weather and climate types. For severe convective storms (tornadoes, hailstorms, and severe thunderstorms), differences in time and space of practices of collecting reports of events make using the reporting database to detect trends extremely difficult. Overall, changes in the frequency of environments favorable for severe thunderstorms have not been statistically significant. For extreme precipitation, there is strong evidence for a nationally averaged upward trend in the frequency and intensity of events. The causes of the observed trends have not been determined with certainty, although there is evidence that increasing atmospheric water vapor may be one factor. For hurricanes and typhoons, robust detection of trends in Atlantic and western North Pacific tropical cyclone (TC) activity is significantly constrained by data heterogeneity and deficient quantification of internal variab...
TL;DR: In this paper, the authors make a case for the increasing significance of climate change in the urban politics of sustainability, and examine their validity in the light of the rapidly changing landscape of urban responses to climate change and the growing academic literature in this field.
Abstract: In our 2005 paper, Rethinking Sustainable Cities, we made a case for the increasing significance of climate change in the urban politics of sustainability. Taking a multilevel governance perspective, we argued that the ‘urban’ governance of climate protection was not confined to a local arena or to the actions of the state, but rather was orchestrated through the interrelations between global, national and local actors across state/non-state boundaries. We revisit these arguments and examine their validity in the light of the rapidly changing landscape of urban responses to climate change and the growing academic literature in this field. We consider in turn: the ways in which climate change is shaping urban agendas; the utility of multilevel governance perspectives for understanding this phenomenon; and the extent to which we can identify a ‘new’ politics of urban climate change governance and its consequent implications for the development of theory and practice in this field.
TL;DR: This work describes a newly developed approach for reproducing the chemical complexity of SSA in a laboratory setting, comprising a unique ocean-atmosphere facility equipped with actual breaking waves and shows SSA size and chemical mixing state are acutely sensitive to the aerosol production mechanism, as well as to the type of biological species present.
Abstract: The production, size, and chemical composition of sea spray aerosol (SSA) particles strongly depend on seawater chemistry, which is controlled by physical, chemical, and biological processes. Despite decades of studies in marine environments, a direct relationship has yet to be established between ocean biology and the physicochemical properties of SSA. The ability to establish such relationships is hindered by the fact that SSA measurements are typically dominated by overwhelming background aerosol concentrations even in remote marine environments. Herein, we describe a newly developed approach for reproducing the chemical complexity of SSA in a laboratory setting, comprising a unique ocean-atmosphere facility equipped with actual breaking waves. A mesocosm experiment was performed in natural seawater, using controlled phytoplankton and heterotrophic bacteria concentrations, which showed SSA size and chemical mixing state are acutely sensitive to the aerosol production mechanism, as well as to the type of biological species present. The largest reduction in the hygroscopicity of SSA occurred as heterotrophic bacteria concentrations increased, whereas phytoplankton and chlorophyll-a concentrations decreased, directly corresponding to a change in mixing state in the smallest (60–180 nm) size range. Using this newly developed approach to generate realistic SSA, systematic studies can now be performed to advance our fundamental understanding of the impact of ocean biology on SSA chemical mixing state, heterogeneous reactivity, and the resulting climate-relevant properties.
TL;DR: Mechanistic experiments suggested that C-H activation is turnover-limiting and irreversible and that insertion of the diazo compound favors electron-deficient substrates.
Abstract: The coupling of O-pivaloyl benzhydroxamic acids with donor/acceptor diazo compounds provides isoindolones in high yield. The reaction tolerates a broad range of benzhydroxamic acids and diazo compounds, including substituted 2,2,2-trifluorodiazoethanes. Mechanistic experiments suggested that C–H activation is turnover-limiting and irreversible and that insertion of the diazo compound favors electron-deficient substrates.
TL;DR: The combined results from KamLAND-Zen and EXO-200 give T(1/2)(0ν)>3.4×10(25) yr at 90% C.L., which corresponds to a Majorana neutrino mass limit of <(120-250) meV based on a representative range of available matrix element calculations.
Abstract: We present results from the first phase of the KamLAND-Zen double-beta decay experiment, corresponding to an exposure of 89.5 kg yr of Xe136. We obtain a lower limit for the neutrinoless double-beta decay half-life of T0ν1/2>1.9×1025 yr at 90% C.L. The combined results from KamLAND-Zen and EXO-200 give T0ν1/2>3.4×1025 yr at 90% C.L., which corresponds to a Majorana neutrino mass limit of ⟨mββ⟩<(120-250) meV based on a representative range of available matrix element calculations. Using those calculations, this result excludes the Majorana neutrino mass range expected from the neutrinoless double-beta decay detection claim in Ge76, reported by a part of the Heidelberg-Moscow Collaboration, at more than 97.5% C.L.
TL;DR: The results advocate for the inclusion of biome-specific soil fauna effects on litter decomposition as a mean to reduce the unexplained variation in large-scale decomposition models.
Abstract: Climate and litter quality have been identified as major drivers of litter decomposition at large spatial scales. However, the role played by soil fauna remains largely unknown, despite its importance for litter fragmentation and microbial activity. We synthesised litterbag studies to quantify the effect sizes of soil fauna on litter decomposition rates at the global and biome scales, and to assess how climate, litter quality and soil fauna interact to determine such rates. Soil fauna consistently enhanced litter decomposition at both global and biome scales (average increment ~ 37%). [corrected]. However, climate and litter quality differently modulated the effects of soil fauna on decomposition rates between biomes, from climate-driven biomes to those where climate effects were mediated by changes in litter quality. Our results advocate for the inclusion of biome-specific soil fauna effects on litter decomposition as a mean to reduce the unexplained variation in large-scale decomposition models.
TL;DR: Natural blends of phytochemicals present in the root exudates can modulate the soil microbiome in the absence of the plant, implying that phenolic compounds act as specific substrates or signaling molecules for a large group of microbial species in the soil.
TL;DR: A comprehensive review of the literature of HEV, PHEV and EV penetration rate studies, their methods, and their recommendations can be found in this paper, where a suite of analytical and computational tools are applied to model the consumer acceptability of these technologies under a wide variety of policy and macroeconomic scenarios.
Abstract: Hybrid, plug-in hybrid and electric vehicles (HEVs, PHEVs, and EVs) are emerging automotive products that have the capability to increase vehicle fuel economy, but at an incremental purchase cost relative to conventional vehicles. In general, their reduced petroleum consumption and improved efficiency provides life cycle economic benefits to consumers, society, automakers, and policymakers. These stakeholders have sought to understand the role of HEVs, PHEVs, and EVs in the future vehicle fleets by estimating the diffusion rate of these technologies into the automotive marketplace. This review presents a comprehensive summary of the literature of HEV, PHEV and EV penetration rate studies, their methods, and their recommendations. These studies have applied a suite of analytical and computational tools to model the consumer acceptability of these technologies under a wide variety of policy and macroeconomic scenarios. The results of these studies are compared and synthesized to understand the strengths and weaknesses of the field and to propose further means for improvement of advanced technology vehicle market modeling exercises. On the basis of this review, the authors recommend that modeling of HEV, PHEV and EV penetration rates should include improved interfaces with consumer surveys, modeling of automakers' actions, federal and state policy and its effect on automotive markets, competition among technologies, market volume, vehicle classifications, and model parameters sensitivity analysis.
TL;DR: It is found that the agricultural and early successional land uses harbored unique soil bacterial communities that exhibited distinct temporal patterns that were likely a product of complex interactions between the soil environment and the more diverse plant community.
Abstract: Although numerous studies have investigated changes in soil microbial communities across space, questions about the temporal variability in these communities and how this variability compares across soils have received far less attention. We collected soils on a monthly basis (May to November) from replicated plots representing three land-use types (conventional and reduced-input row crop agricultural plots and early successional grasslands) maintained at a research site in Michigan, USA. Using barcoded pyrosequencing of the 16S rRNA gene, we found that the agricultural and early successional land uses harbored unique soil bacterial communities that exhibited distinct temporal patterns. α-Diversity, the numbers of taxa or lineages, was significantly influenced by the sampling month with the temporal variability in α-diversity exceeding the variability between land-use types. In contrast, differences in community composition across land-use types were reasonably constant across the 7-month period, suggesting that the time of sampling is less important when assessing β-diversity patterns. Communities in the agricultural soils were most variable over time and the changes were significantly correlated with soil moisture and temperature. Temporal shifts in bacterial community composition within the successional grassland plots were less predictable and are likely a product of complex interactions between the soil environment and the more diverse plant community. Temporal variability needs to be carefully assessed when comparing microbial diversity across soil types and the temporal patterns in microbial community structure can not necessarily be generalized across land uses, even if those soils are exposed to the same climatic conditions.
TL;DR: In this article, a hybrid model that accounts for partitioning between the bulk and surface phases in the context of single parameter representations of cloud condensation nucleus activity is introduced, which allows users of the single parameter model to account for surfactant partitioning by applying minor modifications to existing code.
Abstract: Atmospheric particles can serve as cloud condensation nuclei in the atmosphere The presence of surface active compounds in the particle may affect the critical supersaturation that is required to activate a particle Modelling surfactants in the context of Kohler theory, however, is difficult because surfactant enrichment at the surface implies that a stable radial concentration gradient must exist in the droplet In this study, we introduce a hybrid model that accounts for partitioning between the bulk and surface phases in the context of single parameter representations of cloud condensation nucleus activity The presented formulation incorporates analytical approximations of surfactant partitioning to yield a set of equations that maintain the conceptual and mathematical simplicity of the single parameter framework The resulting set of equations allows users of the single parameter model to account for surfactant partitioning by applying minor modifications to already existing code