bluuebunny/crossref_metadata_2025 huggingface dataset:
Creativity in the Bronze Age: Bringing Archaeological Research into Contemporary Craft Teaching and Learning through a Live Project
Authors: Persad Rachel , Sofaer Joanna
Published: September 2016

The CinBA Live Project sought to engage students of contemporary craft courses in the UK with Bronze Age creativity. We aimed to explore the ways in which the creativity inherent in prehistoric craft may be used as inspiration in contemporary making. It simultaneously offered institutions a unique opportunity to offer a practice‐led, research‐based live project which was distinct to those generally known to be available to art and design institutions. It offered a different experience within this established pedagogical model in art and design education by using the Bronze Age as a source of inspiration for creative practice through practice‐based research in contemporary craft within the framework of an international academic research project, and suggesting new roles for the interpretation of the prehistoric past through creative work. This article reports on the CinBA Live Project. It outlines the context of the opportunity, details our methods of facilitation, describes the activities undertaken by the students and considers the outputs and post‐project impact of the activity.
Simvastatin promotes NPC1‐mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL‐loaded macrophages
Authors: Xu Xiaoyang , Zhang Aolin , Halquist Matthew S. , Yuan Xinxu , Henderson Scott C. , Dewey William L. , Li Pin‐Lan , Li Ningjun , Zhang Fan
Published: September 2016

Statins, 3‐hydroxyl‐3‐methylglutaryl coenzyme A reductase inhibitors, are the first‐line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol‐lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi‐photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low‐density lipoprotein but had little effect in reducing the sizes of cholesteryl ester‐containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome‐compartmentalized cholesterol. Functionally, the egression of free cholesterol from lysosomes attenuated pro‐inflammatory cytokine secretion. It was determined that the reduction of lysosomal free cholesterol buildup by simvastatin was due to the up‐regulation of Niemann‐Pick C1 (NPC1), a lysosomal residing cholesterol transporter. Moreover, the enhanced enzymatic production of 7‐hydroxycholesterol by cytochrome P450 7A1 and the subsequent activation of liver X receptor α underscored the up‐regulation of NPC1. These findings reveal a novel pleiotropic effect of simvastatin in affecting lysosomal cholesterol efflux in macrophages and the associated significance in the treatment of atherosclerosis.
Effects of statistical sampling errors on flood‐damage‐reduction project evaluation
Authors: Su H.‐T. , Tung Y.‐K.
Published: September 2016

Risk‐based decision making of flood‐damage‐reduction (FDR) projects evaluates different design alternatives that have uncertain inundation–reduction benefits and costs. Uncertainties in FDR projects arise from, but are not limited to, the natural randomness of hydrological events, knowledge deficiency in hydrologic models, and the parameters, among others. This study investigates how the flood damage estimation is affected by the epistemic uncertainty resulting from using finite flood data in defining the flood‐frequency relationship and its effects on risk‐based decision making. A Monte Carlo simulation is applied in the study to simulate the epistemic uncertainty associated with the sampling error of the flood magnitude. The model parameter uncertainty is explicitly considered in the estimation of statistical features of flood damage. A recently developed decision rule on the basis of expected opportunity loss (EOL) is applied to the risk‐based evaluation of the relative merits of several competing flood mitigation projects. EOL‐based decision rule has the advantages of considering a decision maker's risk‐aversion attitude and incorporating more complete statistical features of project outcomes, including their correlations. The influence of the model parameter uncertainty on the project evaluation results is examined through an example FDR project with five design alternatives in which flood magnitude follows a Gumbel distribution.
A Model of the Confidence Channel of Fiscal Policy
Authors: GUIMARAES BERNARDO , MACHADO CAIO , RIBEIRO MARCEL
Published: September 2016

This article presents a simple macroeconomic model where government spending affects aggregate demand directly and indirectly, through an expectational channel. Prices are fully flexible and the model is static, so intertemporal issues play no role. There are three important elements in the model: (i) fixed adjustment costs for investment, which create an inaction zone; (ii) noisy idiosyncratic information about the aggregate economy; and (iii) imperfect substitution among private goods and goods provided by the government. An increase in government spending raises demand for private goods and may prevent a coordination failure. The optimal level of government expenditure is high when the desired level of investment is low, which we interpret as a time of low economic activity.
Bank Recapitalization, Regulatory Intervention, and Repayment
Authors: KICK THOMAS , KOETTER MICHAEL , POGHOSYAN TIGRAN
Published: September 2016

We use prudential supervisory data for all German banks during 1994–2010 to test if regulatory interventions affect the likelihood that bailed‐out banks repay capital support. Accounting for the selection bias inherent in nonrandom bank bailouts by insurance schemes and the endogenous administration of regulatory interventions, we show that regulators can increase the likelihood of repayment substantially. An increase in intervention frequencies by one standard deviation increases the annual probability of capital support repayment by 7%. Sturdy interventions, like restructuring orders, are effective, whereas weak measures reduce repayment probabilities. Intervention effects last up to 5 years.
Sex Hormone Decline and Amyloid β Synthesis, Transport and Clearance in the Brain
Authors: Duarte A. C. , Hrynchak M. V. , Gonçalves I. , Quintela T. , Santos C. R. A.
Published: September 2016

Sex hormones (SH) are essential regulators of the central nervous system. The decline in SH levels along with ageing may contribute to compromised neuroprotection and set the grounds for neurodegeneration and cognitive impairments. In Alzheimer's disease, besides other pathological features, there is an imbalance between amyloid β (Aβ) production and clearance, leading to its accumulation in the brain of older subjects. Aβ accumulation is a primary cause for brain inflammation and degeneration, as well as concomitant cognitive decline. There is mounting evidence that SH modulate Aβ production, transport and clearance. Importantly, SH regulate most of the molecules involved in the amyloidogenic pathway, their transport across brain barriers for elimination, and their degradation in the brain interstitial fluid. This review brings together data on the regulation of Aβ production, metabolism, degradation and clearance by SH.
Deciphering Brain Insulin Receptor and Insulin‐Like Growth Factor 1 Receptor Signalling
Authors: Kleinridders A.
Published: September 2016

Insulin receptor (IR) and insulin‐like growth factor 1 receptor (IGF1R) are highly conserved receptor tyrosine kinases that share signalling proteins and are ubiquitously expressed in the brain. Central application of insulin or IGF1 exerts several similar physiological outcomes, varying in strength, whereas disruption of the corresponding receptors in the brain leads to remarkably different effects on brain size and physiology, thus highlighting the unique effects of the corresponding hormone receptors. Central insulin/IGF1 resistance impacts upon various levels of the IR/IGF1R signalling pathways and is a feature of the metabolic syndrome and neurodegenerative diseases such as Alzheimer's disease. The intricacy of brain insulin and IGF1 signalling represents a challenge for the identification of specific IR and IGF1R signalling differences in pathophysiological conditions. The present perspective sheds light on signalling differences and methodologies for specifically deciphering brain IR and IGF1R signalling.
Utopian Passport Control
Authors: Gulddal Jesper
Published: September 2016

The argument presented in this article addresses a conflict that is fundamental to the eighteenth‐century transformation of the novel namely that between the mobility restrictions imposed by the modern state and the novel's traditional dependency on the free mobility of its characters. J. G. Schnabel's Insel Felsenburg is a striking literary manifestation of this conflict. As I argue, the narrative logic of this voluminous and somewhat bizarre novel can only be fully appreciated when taking into account its complex negotiations of mobility and movement control. Marking the confluence of two novelistic traditions, the utopian novel and the adventure novel, it is equally reliant on the settledness and the nomadism of its central characters, the former being the precondition for social order, the latter the basis for the novel's narrative momentum. The structure of the novel results from an attempt to resolve this conflict by channelling mobility into politically and morally acceptable paths – that is, by inventing a literary movement control regime.
Outcomes of emotional support in dating relationships: Relational turbulence or sentiment override?
Authors: SOLOMON DENISE HAUNANI , PRIEM JENNIFER S.
Published: September 2016

This study tests the relational turbulence model by considering how qualities of dating relationships may polarize positive evaluations of partner supportiveness and emotional improvement following an interaction about a stressful experience. Sentiment override, which is the tendency for negative relationship qualities to attenuate positive evaluations of a partner, was evaluated as a competing hypothesis. Using a laboratory‐based observation method, participants completed stressful activities and talked with a dating partner. Results supported the relational turbulence model, such that the positive association between observer ratings of enacted support and emotional improvement increased when turbulence was high. All results for perceived supportiveness were nonsignificant. Relationship satisfaction did not predict either outcome; therefore, the sentiment override hypothesis was not supported.
The N400 elicited by homonyms in puns: Two primes are not better than one
Authors: Dholakia Ayesha , Meade Gabriela , Coch Donna
Published: September 2016

To comprehend a pun involving a homonym (e.g., The prince with a bad tooth got a crown), both meanings of the homonym must be accessed and selected. Previous ERP studies have shown that the N400 reflects lexicosemantic processing, but none have directly investigated the N400 elicited by homonyms in the unique context of puns. Here, N400 priming effects showed that the dual context of puns (e.g., the primes prince and tooth) did not facilitate homonym processing in comparison to single dominant biasing (e.g., The prince with a bad leg got a crown) or subordinate biasing (e.g., The adult with a bad tooth got a crown) conditions. However, homonyms did elicit a less negative N400 (i.e., priming) in the pun condition in comparison to the neutral context condition (e.g., The adult with a bad leg got a crown). These findings are interpreted in terms of the dominant advantage and subordinate bias effect posited by the reordered access model of homonym processing, and in terms of N400 amplitude as an index of how consistently various sources of semantic featural information converge on one lexical item, even when two lexical items must be activated for comprehension.
Providing Context for Ambient Particulate Matter and Estimates of Attributable Mortality
Authors: McClellan Roger O.
Published: September 2016

Four papers on fine particulate matter (PM2.5) by Anenberg et al., Fann et al., Shin et al., and Smith contribute to a growing body of literature on estimated epidemiological associations between ambient PM2.5 concentrations and increases in health responses relative to baseline notes. This article provides context for the four articles, including a historical review of provisions of the U.S. Clean Air Act as amended in 1970, requiring the setting of National Ambient Air Quality Standards (NAAQS) for criteria pollutants such as particulate matter (PM). The substantial improvements in both air quality for PM and population health as measured by decreased mortality rates are illustrated. The most recent revision of the NAAQS for PM2.5 in 2013 by the Environmental Protection Agency distinguished between (1) uncertainties in characterizing PM2.5 as having a causal association with various health endpoints, and as all‐cause mortality, and (2) uncertainties in concentration––excess health response relationships at low ambient PM2.5 concentrations below the majority of annual concentrations studied in the United States in the past. In future reviews, and potential revisions, of the NAAQS for PM2.5, it will be even more important to distinguish between uncertainties in (1) characterizing the causal associations between ambient PM2.5 concentrations and specific health outcomes, such as all‐source mortality, irrespective of the concentrations, (2) characterizing the potency of major constituents of PM2.5, and (3) uncertainties in the association between ambient PM2.5 concentrations and specific health outcomes at various ambient PM2.5 concentrations. The latter uncertainties are of special concern as ambient PM2.5 concentrations and health morbidity and mortality rates approach background or baseline rates.
Multilocus species delimitation in Mesoamerican Scaptotrigona stingless bees (Apidae: Meliponini) supports the existence of cryptic species
Authors: HURTADO–BURILLO MIGUEL , MAY–ITZÁ WILLIAM DE JESÚS , QUEZADA–EÚAN JOSÉ JAVIER G. , DE LA RÚA PILAR , RUIZ CARLOS
Published: September 2016

Accelerating taxonomic knowledge and making accurate species identifications are critically important given the current biodiversity crisis, particularly in biodiversity hotspots such as Mesoamerica. Objective species delimitation that reduces investigator‐driven bias is fundamental to the establishment of appropriate conservation strategies, above all in managed species. Previous morphological and molecular studies on three managed stingless bee species of the genus Scaptotrigona distributed in Mexico (S. mexicana, S. pectoralis and S. hellwegeri) suggested that both S. mexicana and S. hellwegeri are cryptic species complexes. Herein we tested species delimitation by analysing sequence information of five markers (two mitochondrial: cox1 and 16S, and three nuclear: ITS1, EF1‐α, ArgK) within a Bayesian coalescent framework to test the putative species. We obtained two different hypotheses using a Generalized Mixed Yule Coalescent (GMYC) model: four (cox1) and six (16S) species. After the species validation step with the Bayesian species‐delimitation analysis (BPP), we suggest that only S. mexicana is a complex of two species with different distribution (along the Pacific and the Atlantic coasts, respectively). We highly recommend avoiding colony exchange between geographical regions in order to conserve the genetic integrity of both taxa.
Cross‐Border Regional Innovation System Integration: An Analytical Framework
Authors: Makkonen Teemu , Weidenfeld Adi , Williams Allan M.
Published: September 2016

The importance of inter‐regional co‐operation and innovation are widely accepted in the development rhetoric of the European Union. The highlighted importance of both themes in the context of borderlands has recently led to the coining of a new concept, cross‐border regional innovation system. However, little attention has been given to the empirical analysis of the concept. This paper suggests a framework for empirically validating the concept by examining the levels of integration between cross‐border regions. The outcome is a proposed framework that can be operationalised by measurable indicators of cross‐border co‐operation in a regional innovation system setting. The framework was further tested with illustrative empirical cases that demonstrate its feasibility.
Pretransplant prophylactic rituximab to prevent Epstein‐Barr virus (EBV) viremia in EBV‐seronegative kidney transplant recipients from EBV‐seropositive donors: results of a pilot study
Authors: Schachtner Thomas , Reinke Petra
Published: September 2016

Background

Because of the strikingly increased risk of post‐transplant lymphoproliferative disorder (PTLD) in Epstein‐Barr virus (EBV)‐seronegative kidney transplant recipients (KTRs) from EBV‐seropositive donors—EBV(D+R−), special strategies need to be defined to prevent EBV transmission and EBV viremia.

Methods

We studied all KTRs at our center between 2008 and 2012. Seventeen of 402 KTRs (4.2%) were identified as EBV(D+R−), among which 5 KTRs received kidneys from living donors and 12 KTRs from deceased donors. KTRs undergoing living donation were treated with a single dose of rituximab 4 weeks prior to transplantation. Assessment of EBV seroconversion and EBV viremia was performed.

Results

Among 12 EBV‐seronegative KTRs from deceased donors, all 12 KTRs (100%) showed EBV seroconversion, 7 KTRs (58%) showed active EBV viremia, and 1 KTR (8%) developed PTLD. In comparison, 3 of 5 KTRs from living donors, who received pretransplant rituximab, remained EBV‐seronegative post transplantation, and no KTR developed EBV viremia (P<.05). All KTRs who received pretransplant rituximab showed excellent allograft function, with no increase in infections or malignancies.

Conclusions

Our data suggest that rituximab‐mediated elimination of B cells may prevent transmission of EBV to the recipient, as EBV persistence requires the establishment of a latent infection in recipient B cells. Pretransplant rituximab may prove useful to prevent primary EBV infection in EBV‐seronegative KTRs.
The impact of directly acting antivirals on the enzymatic liver function of liver transplant recipients with recurrent hepatitis C
Authors: Raschzok Nathanael , Schott Eckart , Reutzel‐Selke Anja , Damrah Iman , Gül‐Klein Safak , Strücker Benjamin , Sauer Igor Maximilian , Pratschke Johann , Eurich Dennis , Stockmann Martin
Published: September 2016

Background

The new directly acting antivirals (DAAs) enable all‐oral interferon‐free treatment of chronic hepatitis C virus (HCV) infection. We here investigated the effect of DAAs on the enzymatic liver function of liver transplant recipients with recurrent hepatitis C.

Methods

Twenty‐one patients with elevated liver enzymes or advanced fibrosis/compensated cirrhosis caused by recurrent HCV were treated with sofosbuvir either in combination with simeprevir, or in combination with ribavirin or daclatasvir with or without ribavirin for 12 weeks. Biochemical parameters, tacrolimus trough levels, and the maximal liver function capacity (LiMAx) were measured monthly during the treatment and 12 weeks after the end of treatment.

Results

All patients achieved sustained virological response 12 weeks after the end of the treatment. The transaminases and cholestasis parameters normalized until week 8 of treatment. The mean LiMAx (normal ranges >315 μg/kg/h) increased from 344±142 μg/kg/h before treatment to 458±170 μg/kg/h (P<.0001) at the 12‐week follow‐up. In parallel, the tacrolimus trough level to dose ratio decreased from 4.68 down to 2.72 (P=.0004).

Conclusion

Antiviral treatment with DAAs enabled sustained elimination of recurrent HCV in liver transplant recipients and was associated with a significant improvement of the enzymatic liver function.
Monitoring clinical trials: a practical guide
Authors: Molloy Síle F. , Henley Patricia
Published: September 2016

This article describes the processes and procedures involved in planning, conducting and reporting monitoring activities for large Clinical Trials of Investigational Medicinal Products (CTIMPs), focusing on those conducted in resource‐limited settings.
A Structural Dynamic Model Inversion-Based Technique to Characterize Impacts to a Full-Scale and Operational Helicopter Rotor Blade
Authors: Hylton Blake , Crandall Andrew , Koester Dave , Bouquillon Brian , Meckl Peter , Adams Douglas
Published: September 2016

The incorporation of real-time structural health monitoring has the potential to substantially reduce the inspection burden of advanced composite rotor blades, particularly if impacts can be detected and characterized using operational data. Data-driven impact identification techniques, such as those applied in this work, require that a structural dynamic model of blade frequency response functions (FRFs) be developed for the operational environment. However, the operational characteristics of the rotor system are not accurately described by a model developed and validated in a nonrotating environment. The discrepancies are predominately due to two sources: the change in the blade root boundary condition and the presence of a centrifugal force. This research demonstrates an analytical methodology to compensate for the first of these effects. Derivations of this method are included, as well as analytical and experimental results. Additionally, the theory and experimental results are presented for an approach by which planar impact area and impactor stiffness may be estimated. Applying these techniques, impact location estimation accuracy was improved from 51.6% to 94.2%. Impacts produced by objects of 2–in. diameter were demonstrated to be distinguishable from those of 1 in. or less diameter. Finally, it was demonstrated that the impacts by objects of metallic material were distinguishable from those of rubber material, and that such differentiation was robust to impactor size and impact force magnitude.
Three-Dimensional-Printed Multistable Mechanical Metamaterials With a Deterministic Deformation Sequence
Authors: Che Kaikai , Yuan Chao , Wu Jiangtao , Jerry Qi H. , Meaud Julien
Published: September 2016

Multistable mechanical metamaterials are materials that have multiple stable configurations. The geometrical changes caused by the transition of the metamaterial from one stable state to another, could be exploited to obtain multifunctional and programmable materials. As the stimulus amplitude is varied, a multistable metamaterial goes through a sequence of stable configurations. However, this sequence (which we will call the deformation sequence) is unpredictable if the metamaterial consists of identical unit cells. This paper proposes to use small variations in the unit cell geometry to obtain a deterministic deformation sequence for one type of multistable metamaterial that consists of bistable unit cells. Based on an analytical model for a single unit cell and on the minimization of the total strain energy, a rigorous theoretical model is proposed to analyze the nonlinear mechanics of this type of metamaterials and to inform the designs. The proposed theoretical model is able to accurately predict the deformation sequence and the stress–strain curves that are observed in the finite-element simulations with an elastic constitutive model. A deterministic deformation sequence that matches the sequence predicted by the theory and finite-element simulations is obtained in experiments with 3D-printed samples. Furthermore, an excellent quantitative agreement between simulations and experiments is obtained once a viscoelastic constitutive model is introduced in the finite-element model.
Optimal Interval for Success in Judo World-Ranking Competitions
Authors: Franchini Emerson , Takito Monica Y. , da Silva Rodrigo M. , Shiroma Seihati A. , Wicks Lance , Julio Ursula F.
Published: September 2016

Purpose:

To determine the optimal interval between competitions for success in the different events of the judo world tour.

Methods:

A total of 20,916 female and 29,900 male competition participations in the judo world-tour competitions held between January 2009 and December 2015 were analyzed, considering the dependent variable, winning a medal, and the independent variables, levels of competition.

Results:

There was an increased probability of winning a medal when the interval was in the 10- to 13-wk range for both male and female athletes competing at Grand Prix, Continental-Championship, and World-Championship events, whereas for Grand Slam, only men had an increased probability of winning a medal in this interval range. Furthermore, men had increased probability of podium positions in Continental Championship, World Master, and Olympic Games when the interval was longer than 14 wk.

Conclusion:

Optimal interval period between successive competitions varies according to competition level and sex; shorter intervals (6–9 wk) were better for female athletes competing at the lowest competition level (Continental Open), but for most of the competitions, the 10- to 13-wk interval was detected as optimal for both male and female athletes (Grand Prix, Continental Championship, and World Championship), whereas for the ranking-based qualified male competitions (ie, Masters and Olympic Games), a longer period (>14 wk) is needed.
Anthropometrics and Body Composition in East African Runners: Potential Impact on Performance
Authors: Mooses Martin , Hackney Anthony C.
Published: September 2016

Maximal oxygen uptake (V̇O2max), fractional utilization of V̇O2max during running, and running economy (RE) are crucial factors for running success for all endurance athletes. Although evidence is limited, investigations of these key factors indicate that East Africans’ superiority in distance running is largely due to a unique combination of these factors. East African runners appear to have a very high level of RE most likely associated, at least partly, with anthropometric characteristics rather than with any specific metabolic property of the working muscle. That is, evidence suggest that anthropometrics and body composition might have important parameters as determinants of superior performance of East African distance runners. Regrettably, this role is often overlooked and mentioned as a descriptive parameter rather than an explanatory parameter in many research studies. This brief review article provides an overview of the evidence to support the critical role anthropometrics and body composition has on the distance running success of East African athletes. The structural form and shape of these athletes also has a downside, because having very low BMI or body fat increases the risk for relative energy deficiency in sport (RED-S) conditions in both male and female runners, which can have serious health consequences.
Early pre-Hispanic use of indigo blue in Peru
Authors: Splitstoser Jeffrey C. , Dillehay Tom D. , Wouters Jan , Claro Ana
Published: September 2016

Cotton textiles from the Andean site of Huaca Prieta were decorated with the world’s earliest identified use of indigo blue.
The elementary representation of spatial and color vision in the human retina
Authors: Sabesan Ramkumar , Schmidt Brian P. , Tuten William S. , Roorda Austin
Published: September 2016

The origins of spatial and color vision in the human retina.
Pyre experiments cast doubt on students' fate
Authors: Wade Lizzie
Published: September 2016

Findings suggest investigators in Mexico should take new tack in unsolved case.
Study takes sharp tusk to effort to legalize ivory trade
Authors: Morell Virginia
Published: September 2016

Slow-growing elephants can't be harvested sustainably.
The plant engineer
Authors: Pennisi Elizabeth
Published: September 2016

Dan Voytas has worked tirelessly to make targeted genome editing of plants a reality.
When is a GM plant not a GM plant?
Authors: Pennisi Elizabeth
Published: September 2016

New genome-editing technologies have confused the regulatory picture for genetically modified plants.
The nitrogen fix
Authors: Stokstad Erik
Published: September 2016

Few projects in plant biotechnology are harder, or promise a greater payoff, than enabling crops to make their own nitrogen fertilizer.
Plant metabolism, the diverse chemistry set of the future
Authors: Wurtzel Eleanore T. , Kutchan Toni M.
Published: September 2016

New technologies are redefining how plant biology will meet societal challenges in health, nutrition, agriculture, and energy. Rapid and inexpensive genome and transcriptome sequencing is being exploited to discover biochemical pathways that provide tools needed for synthetic biology in both plant and microbial systems. Metabolite detection at the cellular and subcellular levels is complementing gene sequencing for pathway discovery and metabolic engineering. The crafting of plant and microbial metabolism for the synthetic biology platforms of tomorrow will require precise gene editing and delivery of entire complex pathways. Plants sustain life and are key to discovery and development of new medicines and agricultural resources; increased research and training in plant science will accelerate efforts to harness the chemical wealth of the plant kingdom.
The plant lipidome in human and environmental health
Authors: Horn Patrick J. , Benning Christoph
Published: September 2016

Lipids and oils derived from plant and algal photosynthesis constitute much of human daily caloric intake and provide the basis for high-energy bioproducts, chemical feedstocks for countless applications, and even fossil fuels over geological time scales. Sustainable production of high-energy compounds from plants is essential to preserving fossil fuel sources and ensuring the well-being of future generations. As a result of progress in basic research on plant and algal lipid metabolism, in combination with advances in synthetic biology, we can now tailor plant lipids for desirable biological, physical, and chemical properties. We highlight recent advances in plant lipid translational biology and discuss untapped areas of research that might expand the application of plant lipids.
Bats perceptually weight prey cues across sensory systems when hunting in noise
Authors: Gomes D. G. E. , Page R. A. , Geipel I. , Taylor R. C. , Ryan M. J. , Halfwerk W.
Published: September 2016

Anthropogenic noise can interfere with environmental information processing and thereby reduce survival and reproduction. Receivers of signals and cues in particular depend on perceptual strategies to adjust to noisy conditions. We found that predators that hunt using prey sounds can reduce the negative impact of noise by making use of prey cues conveyed through additional sensory systems. In the presence of masking noise, but not in its absence, frog-eating bats preferred and were faster in attacking a robotic frog emitting multiple sensory cues. The behavioral changes induced by masking noise were accompanied by an increase in active localization through echolocation. Our findings help to reveal how animals can adapt to anthropogenic noise and have implications for the role of sensory ecology in driving species interactions.
Quantifying the impact of molecular defects on polymer network elasticity
Authors: Zhong Mingjiang , Wang Rui , Kawamoto Ken , Olsen Bradley D. , Johnson Jeremiah A.
Published: September 2016

Elasticity, one of the most important properties of a soft material, is difficult to quantify in polymer networks because of the presence of topological molecular defects in these materials. Furthermore, the impact of these defects on bulk elasticity is unknown. We used rheology, disassembly spectrometry, and simulations to measure the shear elastic modulus and count the numbers of topological “loop” defects of various order in a series of polymer hydrogels, and then used these data to evaluate the classical phantom and affine network theories of elasticity. The results led to a real elastic network theory (RENT) that describes how loop defects affect bulk elasticity. Given knowledge of the loop fractions, RENT provides predictions of the shear elastic modulus that are consistent with experimental observations.
Spin- and density-resolved microscopy of antiferromagnetic correlations in Fermi-Hubbard chains
Authors: Boll Martin , Hilker Timon A. , Salomon Guillaume , Omran Ahmed , Nespolo Jacopo , Pollet Lode , Bloch Immanuel , Gross Christian
Published: September 2016

The repulsive Hubbard Hamiltonian is one of the foundational models describing strongly correlated electrons and is believed to capture essential aspects of high-temperature superconductivity. Ultracold fermions in optical lattices allow for the simulation of the Hubbard Hamiltonian with control over kinetic energy, interactions, and doping. A great challenge is to reach the required low entropy and to observe antiferromagnetic spin correlations beyond nearest neighbors, for which quantum gas microscopes are ideal. Here, we report on the direct, single-site resolved detection of antiferromagnetic correlations extending up to three sites in spin-1/2 Hubbard chains, which requires entropies per particle well below
s
* = ln(2). The simultaneous detection of spin and density opens the route toward the study of the interplay between magnetic ordering and doping in various dimensions.
The next green movement: Plant biology for the environment and sustainability
Authors: Jez Joseph M. , Lee Soon Goo , Sherp Ashley M.
Published: September 2016

From domestication and breeding to the genetic engineering of crops, plants provide food, fuel, fibers, and feedstocks for our civilization. New research and discoveries aim to reduce the inputs needed to grow crops and to develop plants for environmental and sustainability applications. Faced with population growth and changing climate, the next wave of innovation in plant biology integrates technologies and approaches that span from molecular to ecosystem scales. Recent efforts to engineer plants for better nitrogen and phosphorus use, enhanced carbon fixation, and environmental remediation and to understand plant-microbiome interactions showcase exciting future directions for translational plant biology. These advances promise new strategies for the reduction of inputs to limit environmental impacts and improve agricultural sustainability.
Observation of spatial charge and spin correlations in the 2D Fermi-Hubbard model
Authors: Cheuk Lawrence W. , Nichols Matthew A. , Lawrence Katherine R. , Okan Melih , Zhang Hao , Khatami Ehsan , Trivedi Nandini , Paiva Thereza , Rigol Marcos , Zwierlein Martin W.
Published: September 2016

Strong electron correlations lie at the origin of high-temperature superconductivity. Its essence is believed to be captured by the Fermi-Hubbard model of repulsively interacting fermions on a lattice. Here we report on the site-resolved observation of charge and spin correlations in the two-dimensional (2D) Fermi-Hubbard model realized with ultracold atoms. Antiferromagnetic spin correlations are maximal at half-filling and weaken monotonically upon doping. At large doping, nearest-neighbor correlations between singly charged sites are negative, revealing the formation of a correlation hole, the suppressed probability of finding two fermions near each other. As the doping is reduced, the correlations become positive, signaling strong bunching of doublons and holes, in agreement with numerical calculations. The dynamics of the doublon-hole correlations should play an important role for transport in the Fermi-Hubbard model.
GM crops—lessons from medicine
Authors: Hunter Jackie , Duff Gordon
Published: September 2016

Earlier this year, the U.S. National Academy of Sciences released a report on genetically engineered crops that is comprehensive but offers few recommendations in terms of regulatory guidance. Although it acknowledges that a process-based regulatory system is becoming less technically feasible, the report suggests that regulators focus on safety aspects of technology when considering approval. We believe that products of new technologies should be regulated not only on the basis of their benefit-risk profiles, but also on their societal context and need.
Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer
Authors: Mulhall Robert M. , Brehony Carina , O'Connor Lois , Meyler Kenneth , Jolley Keith A. , Bray James , Bennett Desiree , Maiden Martin C. J. , Cunney Robert
Published: September 2016

A carriage study was undertaken (
n
= 112) to ascertain the prevalence of
Neisseria
spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (
n
= 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled
de novo
and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (
n
= 8/14), persisting for at least 44 months, likely driven by the high population density of houses (
n
= 67/112) and trailers (
n
= 45/112). Carriage for
Neisseria meningitidis
(
P
< 0.05) and
Neisseria lactamica
(
P
< 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%,
n
= 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by
Neisseria lactamica
and
Neisseria meningitidis
. One HGT event resulted in the acquisition of 26 consecutive
N. lactamica
alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.
Clinical Significance of Commensal Gram-Positive Rods Routinely Isolated from Patient Samples
Authors: Leal Sixto M. , Jones Melissa , Gilligan Peter H.
Published: September 2016

Commensal bacteria from the skin and mucosal surfaces are routinely isolated from patient samples and considered contaminants. The majority of these isolates are catalase-positive Gram-positive rods from multiple genera routinely classified as diphtheroids. These organisms can be seen upon Gram staining of clinical specimens or can be isolated as the predominant or pure species in culture, raising
a priori
suspicion of a possible involvement in infection. With the development and adoption of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), suspicious isolates are now routinely identified to the species level. In this study, we performed a retrospective data review (2012 to 2015) and utilized site-specific laboratory criteria and chart reviews to identify species within the diphtheroid classification representative of true infection versus contamination. Our data set included 762 isolates from 13 genera constituting 41 bacterial species. Only 18% represented true infection, and 82% were deemed contaminants. Clinically significant isolates were identified in anaerobic wounds (18%), aerobic wounds (30%), blood (5.5%), urine (22%), cerebrospinal fluid (24%), ophthalmologic cultures (8%), and sterile sites (20%). Organisms deemed clinically significant included multiple
Actinomyces
species in wounds,
Propionibacterium
species in joints and cerebrospinal fluid associated with central nervous system hardware,
Corynebacterium kroppenstedtii
(100%) in breast, and
Corynebacterium striatum
in multiple sites. Novel findings include clinically significant urinary tract infections by
Actinomyces neuii
(21%) and
Corynebacterium aurimucosum
(21%). Taken together, these findings indicate that species-level identification of diphtheroids isolated with
a priori
suspicion of infection is essential to accurately determine whether an isolate belongs to a species associated with specific types of infection.
Whole-Genome Multilocus Sequence Typing of Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae
Authors: Kluytmans-van den Bergh Marjolein F. Q. , Rossen John W. A. , Bruijning-Verhagen Patricia C. J. , Bonten Marc J. M. , Friedrich Alexander W. , Vandenbroucke-Grauls Christina M. J. E. , Willems Rob J. L. , Kluytmans Jan A. J. W.
Published: September 2016

Molecular typing has become indispensable in the detection of nosocomial transmission of bacterial pathogens and the identification of sources and routes of transmission in outbreak settings, but current methods are labor-intensive, are difficult to standardize, or have limited resolution. Whole-genome multilocus sequence typing (wgMLST) has emerged as a whole-genome sequencing (WGS)-based gene-by-gene typing method that may overcome these limitations and has been applied successfully for several species in outbreak settings. In this study, genus-, genetic-complex-, and species-specific wgMLST schemes were developed for
Citrobacter
spp., the
Enterobacter cloacae
complex,
Escherichia coli
,
Klebsiella oxytoca
, and
Klebsiella pneumoniae
and used to type a national collection of 1,798 extended-spectrum-beta-lactamase-producing
Enterobacteriaceae
(ESBL-E) isolates obtained from patients in Dutch hospitals. Genus-, genetic-complex-, and species-specific thresholds for genetic distance that accurately distinguish between epidemiologically related and unrelated isolates were defined for
Citrobacter
spp., the
E. cloacae
complex,
E. coli
, and
K. pneumoniae
. wgMLST was shown to have higher discriminatory power and typeability than
in silico
MLST. In conclusion, the wgMLST schemes developed in this study facilitate high-resolution WGS-based typing of the most prevalent ESBL-producing species in clinical practice and may contribute to further elucidation of the complex epidemiology of antimicrobial-resistant
Enterobacteriaceae
. wgMLST opens up possibilities for the creation of a Web-accessible database for the global surveillance of ESBL-producing bacterial clones.
Comparison of Minocycline Susceptibility Testing Methods for Carbapenem-Resistant Acinetobacter baumannii
Authors: Wang Peng , Bowler Sarah L. , Kantz Serena F. , Mettus Roberta T. , Guo Yan , McElheny Christi L. , Doi Yohei
Published: September 2016

Treatment options for infections due to carbapenem-resistant
Acinetobacter baumannii
are extremely limited. Minocycline is a semisynthetic tetracycline derivative with activity against this pathogen. This study compared susceptibility testing methods that are used in clinical microbiology laboratories (Etest, disk diffusion, and Sensititre broth microdilution methods) for testing of minocycline, tigecycline, and doxycycline against 107 carbapenem-resistant
A. baumannii
clinical isolates. Susceptibility rates determined with the standard broth microdilution method using cation-adjusted Mueller-Hinton (MH) broth were 77.6% for minocycline and 29% for doxycycline, and 92.5% of isolates had tigecycline MICs of ≤2 μg/ml. Using MH agar from BD and Oxoid, susceptibility rates determined with the Etest method were 67.3% and 52.3% for minocycline, 21.5% and 18.7% for doxycycline, and 71% and 29.9% for tigecycline, respectively. With the disk diffusion method using MH agar from BD and Oxoid, susceptibility rates were 82.2% and 72.9% for minocycline and 34.6% and 34.6% for doxycycline, respectively, and rates of MICs of ≤2 μg/ml were 46.7% and 23.4% for tigecycline. In comparison with the standard broth microdilution results, very major rates were low (∼2.8%) for all three drugs across the methods, but major error rates were higher (∼5.6%), especially with the Etest method. For minocycline, minor error rates ranged from 14% to 37.4%. For tigecycline, minor error rates ranged from 6.5% to 69.2%. The majority of minor errors were due to susceptible results being reported as intermediate. For minocycline susceptibility testing of carbapenem-resistant
A. baumannii
strains, very major errors are rare, but major and minor errors overcalling strains as intermediate or resistant occur frequently with susceptibility testing methods that are feasible in clinical laboratories.
A Library of Infectious Hepatitis C Viruses with Engineered Mutations in the E2 Gene Reveals Growth-Adaptive Mutations That Modulate Interactions with Scavenger Receptor Class B Type I
Authors: Zuiani Adam , Chen Kevin , Schwarz Megan C. , White James P. , Luca Vincent C. , Fremont Daved H. , Wang David , Evans Matthew J. , Diamond Michael S.
Published: September 2016

While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties.

IMPORTANCE
Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability.