bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Transcriptome and Promoter Architecture of the African Swine Fever Virus
Authors: Cackett Gwenny , Matelska Dorota , Sýkora Michal , Portugal Raquel , Malecki Michal , Bähler Jürg , Dixon Linda , Werner Finn 
Published: November 2019

AbstractThe African Swine Fever Virus causes haemorrhagic fever in domestic pigs and presents the biggest global threat to animal farming in recorded history. Despite its importance, very little is known the mechanisms and temporal regulation of transcription in ASFV. Here we report the first detailed viral transcriptome analysis of ASFV during early and late infection ofVerocells. In addition to total RNA sequencing, we have characterised the transcription start sites and transcription termination sites at nucleotide-resolution, revealing the distinct DNA consensus motifs of early and late promoters, as well as the sequence determinants for transcription termination. ASFV can utilise alternative promoters to generate distinct proteins from the same transcription unit that differ with respect to the polypeptide N-terminus. Finally, our results reveal that the ASFV-RNAP undergoes transcript slippage at the 5’ end of transcription units that in a promoter sequence-specific manner results in the addition of 5’-AT and 5’-ATAT tails to mRNAs.
Testing Darwin’s naturalization conundrum based on taxonomic, phylogenetic and functional dimensions of vascular plants
Authors: Pinto-Ledezma Jesús N. , Villalobos Fabricio , Reich Peter B. , Larkin Daniel J. , Cavender-Bares Jeannine 
Published: November 2019

AbstractCharles Darwin posited two alternative hypotheses to explain the success of nonnative species based on their relatedness to incumbent natives: coexistence between them should be (i) more likely with greater relatedness (due to trait similarity that correlates with better matching to the environment), or (ii) less likely (due to biotic interference, such as competition). The paradox raised by the opposing predictions of these two hypotheses has been termed ‘Darwin’s naturalization conundrum’ (DNC). Using plant communities measured repeatedly over a 31-year time span across an experimental fire gradient in an oak savanna (Minnesota, USA) we evaluated the DNC by explicitly incorporating taxonomic, functional and phylogenetic information. Our approach was based on ‘focal-species’ such that the taxonomic, functional and phylogenetic structure of species co-occurring with a given nonnative species in local communities was quantified. We found three main results: first, nonnatives colonizers tended to co-occur most with closely related incumbent natives in recipient communities, except in the extreme ends of the fire gradient (i.e., communities with no fire and those subjected to high fire frequencies); second, with increasing fire frequency, nonnative species were functionally more similar to native species in recipient communities; third, functional similarity of co-occurring nonnatives and natives in recipient communities showed a consistent pattern over time, but the phylogenetic similarity shifted over time, suggesting that external forces (e.g., climate variability) are also relevant in driving the phylogenetic relatedness of nonnatives to natives in invaded communities. Our results provide insights for understanding the invasion dynamics across environmental gradients and highlight the importance of evaluating different dimensions of biodiversity in order to produce more powerful evaluations of species co-occurrence at different spatial and temporal scales.
Antagonistic odor interactions in olfactory sensory neurons are widespread in freely breathing mice
Authors: Zak Joseph D. , Reddy Gautam , Vergassola Massimo , Murthy Venkatesh N. 
Published: November 2019

AbstractOdor landscapes contain complex blends of discrete molecules that each activate unique, overlapping populations of olfactory sensory neurons (OSNs). Despite the presence of hundreds of OSN subtypes in many animals, the overlapping nature of odor inputs may lead to saturation of neural responses at the early stages of stimulus encoding. Information loss due to saturation could be mitigated by normalizing mechanisms such as antagonism at the level of receptor-ligand interactions, whose existence and prevalence remains uncertain. By imaging OSN axon terminals in olfactory bulb glomeruli as well as OSN cell bodies within the olfactory epithelium in freely breathing mice, we found widespread antagonistic interactions in binary odor mixtures. In complex mixtures of up to 12 odorants, antagonistic interactions became stronger and more prevalent with increasing mixture complexity. Therefore, antagonism is a remarkably common feature of odor mixture encoding in olfactory sensory neurons and helps in normalizing activity to reduce saturation.
Comparative genomics reveals signature regions used to develop a robust and sensitive multiplex TaqMan real-time qPCR assay to detect the genus Dickeya and Dickeya dianthicola
Authors: Dobhal Shefali , Boluk Gamze , Babler Brooke , Stulberg Michael J. , Rascoe John , Nakhla Mark , Chapman Toni A. , Crockford Alex B. , Melzer Michael , Alvarez Anne M. , Arif Mohammad 
Published: November 2019

AbstractAimsDickeya species are high consequence plant pathogenic bacteria listed among the quarantine pathogens of the European Union; associated with potato disease outbreaks and subsequent economic losses worldwide. Early, accurate, and reliable detection of Dickeya spp. is needed to prevent establishment and further dissemination of this pathogen. Therefore, a multiplex TaqMan qPCR was developed for sensitive detection of Dickeya spp. and specifically, D. dianthicola.Methods and ResultsA signature genomic region for the genus Dickeya (mglA/mglC) and unique genomic region for D. dianthicola (alcohol dehydrogenase) were identified using a whole genome based comparative genomics approach. The developed multiplex TaqMan qPCR was validated using extensive inclusivity and exclusivity panels, and naturally/artificially infected samples to confirm broad range detection capability and specificity. Both sensitivity and spiked assays showed detection limit of 10 fg DNA.ConclusionThe developed multiplex assay is sensitive and reliable to detect Dickeya spp. and D. dianthicola with no false positives or false negatives. It was able to detect mixed infection from naturally and artificially infected plant materials.Significance and ImpactThe developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding program. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.
Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis
Authors: Kusnadi E. P. , Trigos A. S. , Cullinane C. , Goode D. L. , Larsson O. , Devlin J. R. , Chan K. T. , De Souza D. P. , McConville M. J. , McArthur G. A. , Thomas G. , Sanij E. , Poortinga G. , Hannan R. D. , Hannan K. M. , Kang J. , Pearson R. B. 
Published: November 2019

AbstractElevated ribosome biogenesis in oncogene-driven cancers is commonly targeted by DNA-damaging cytotoxic drugs. Our first-in-human trial of CX-5461, a novel, less genotoxic agent that specifically inhibits ribosome biogenesis via suppression of RNA Polymerase I (Pol I) transcription, revealed single agent efficacy in refractory blood cancers. Despite this clinical response, patients were not cured. In parallel, we demonstrated a marked improvement in thein vivoefficacy of CX-5461 in combination with PI3K/AKT/mTORC1 pathway inhibitors. Here we show that this improved efficacy is associated with specific suppression of translation of mRNAs encoding regulators of cellular metabolism. Importantly, acquired resistance to this co-treatment is driven by translational re-wiring that results in dysregulated cellular metabolism and induction of a cAMP-dependent pathway critical for the survival of blood cancers including lymphoma and acute myeloid leukemia. Our studies identify the molecular mechanisms underpinning the response of blood cancers to selective ribosome biogenesis inhibitors and identify metabolic vulnerabilities that will facilitate the rational design of more effective regimens for Pol I-directed therapies.
Modality-specific and multisensory mechanisms of spatial attention and expectation
Authors: Zuanazzi Arianna , Noppeney Uta 
Published: November 2019

AbstractIn our natural environment, the brain needs to combine signals from multiple sensory modalities into a coherent percept. While spatial attention guides perceptual decisions by prioritizing processing of signals that are task-relevant, spatial expectations encode the probability of signals over space. Previous studies have shown that behavioral effects of spatial attention generalize across sensory modalities. However, because they manipulated spatial attention as signal probability over space, these studies could not dissociate attention and expectation or assess their interaction.In two experiments, we orthogonally manipulated spatial attention (i.e., task-relevance) and expectation (i.e., signal probability) selectively in one sensory modality (i.e., primary modality) (experiment 1: audition, experiment 2: vision) and assessed their effects on primary and secondary sensory modalities in which attention and expectation were held constant.Our results show behavioral effects of spatial attention that are comparable for audition and vision as primary modalities; yet, signal probabilities were learnt more slowly in audition, so that spatial expectations were formed later in audition than vision. Critically, when these differences in learning between audition and vision were accounted for, both spatial attention and expectation affected responses more strongly in the primary modality in which they were manipulated, and generalized to the secondary modality only in an attenuated fashion. Collectively, our results suggest that both spatial attention and expectation rely on modality-specific and multisensory mechanisms.
Modulating the cellular context broadly reshapes the mutational landscape of a model enzyme
Authors: Thompson Samuel , Zhang Yang , Ingle Christine , Reynolds Kimberly A. , Kortemme Tanja 
Published: November 2019

AbstractProtein mutational landscapes are shaped by the cellular environment, but key factors and their quantitative effects are often unknown. Here we show that Lon, a quality control protease naturally absent in common E. coli expression strains, drastically reshapes the mutational landscape of the metabolic enzyme dihydrofolate reductase (DHFR). Selection under conditions that resolve highly active mutants reveals that 23.3% of all single point mutations in DHFR are advantageous in the absence of Lon, but advantageous mutations are largely suppressed when Lon is reintroduced. Protein stability measurements demonstrate extensive activity-stability tradeoffs for the advantageous mutants and provide a mechanistic explanation for Lon’s widespread impact. Our findings suggest possibilities for tuning mutational landscapes by modulating the cellular environment, with implications for protein design and combatting antibiotic resistance.
Phenotypic and physiological responses to salt exposure inSorghumreveal diversity among domesticated landraces
Authors: Henderson Ashley N. , Crim Philip M. , Cumming Jonathan R. , Hawkins Jennifer S. 
Published: November 2019

ABSTRACTSoil salinity negatively impacts plant function, development, and yield.Sorghum bicoloris a staple crop known to be drought tolerant, to have adapted to a variety of conditions, and to contain significant standing genetic diversity, making it an exemplary species to study phenotypic and physiological variation in salinity tolerance. In our study, a diverse group of sorghum landraces and accessions was first rank-ordered for salinity tolerance and then individuals spanning a wide range of response were analyzed for foliar proline and ion accumulation. We found that, while proline is often a good indicator of osmotic adjustment and is historically associated with increased salt tolerance, proline accumulation in sorghum reflects stress-response injury rather than acclimation. When combining ion profiles with growth responses and stress tolerance indices, the variation observed in tolerance was similarly not a sole result of Na+accumulation, but rather reflected accession-specific mechanisms that may integrate these and other metabolic responses. When we compared variation in tolerance to phylogenetic relationships, we conclude that the most parsimonious explanation for the variation observed among accessions is that salinity tolerance was acquired early during domestication and was subsequently maintained or lost in diverged lineages during improvement in areas that vary in soil salinity.
Preference and switching in the Kill-the-Winner functional response: Diversity, size structure, and synergistic grazing in plankton models
Authors: Archibald Kevin M. , Sosik Heidi M. , Neubert Michael G. 
Published: November 2019

AbstractGrazing by zooplankton can maintain diversity in phytoplankton communities by allowing coexistence between competitors in situations that would otherwise lead to competitive exclusion. In mathematical models, grazing is represented by a functional response that describes the consumption rate by an individual zooplankter as a function of phytoplankton concentration. Since its initial description, the Kill-the-Winner functional response has been increasingly adopted for large-scale biogeochemical modeling. Here, we analyze how two properties of the Kill-the-Winner functional response—preference and switching—interact to promote coexistence and increase diversity in two simple models: a diamond-shaped nutrient-phytoplankton-zooplankton model and a size-structured phytoplankton community model. We found that, compared to preference, switching leads to coexistence and increased diversity over a much wider range of environmental conditions (nutrient supply and mixing rate). In the absence of switching, preference only allows for coexistence within the narrow range of environmental conditions where the preference is precisely balanced against the competitive difference between phytoplankton types. We also explored a counterintuitive aspect of the Kill-the-Winner functional response that we have termed “synergistic grazing”. Synergistic grazing occurs when the grazing rate on one phytoplankton type increases as the biomass of an alternative phytoplankton type increases. This unrealistic effect is most evident when switching is strong and when zooplankton have a preference for the weaker competitor.
Queue-based features for dynamic waiting time prediction in emergency department
Authors: Benevento Elisabetta , Aloini Davide , Squicciarini Nunzia , Dulmin Riccardo , Mininno Valeria 
Published: November 2019

Purpose
The purpose of this study is twofold: exploring new queue-based variables enabled by process mining and evaluating their impact on the accuracy of waiting time prediction. Such queue-based predictors that capture the current state of the emergency department (ED) may lead to a significant improvement in the accuracy of the prediction models.

Design/methodology/approach
Alongside the traditional variables influencing ED waiting time, the authors developed new queue-based predictors exploiting process mining. Process mining techniques allowed the authors to discover the actual patient-flow and derive information about the crowding level of the activities. The proposed predictors were evaluated using linear and nonlinear learning techniques. The authors used real data from an ED.

Findings
As expected, the main results show that integrating the set of predictors with queue-based variables significantly improves the accuracy of waiting time prediction. Specifically, mean square error values were reduced by about 22 and 23 per cent by applying linear and nonlinear learning techniques, respectively.

Practical implications
Accurate estimates of waiting time can enable the ED systems to prevent overcrowding e.g. improving the routing of patients in EDs and managing more efficiently the resources. Providing accurate waiting time information also can lead to decreased patients’ dissatisfaction and elopement.

Originality/value
The novelty of the study relies on the attempt to derive queue-based variables reporting the crowding level of the activities within the ED through process mining techniques. Such information is often unavailable or particularly difficult to extract automatically, due to the characteristics of ED processes.
Subsidiary strategy and managers’ perceptions of distance to foreign markets
Authors: Antunes Isabel Cristina Martins , Barandas Hortênsia Gouveia , Martins Francisco Vitorino 
Published: November 2019

Purpose
The purpose of this paper is to examine how headquarters’ managers perceive – cultural, administrative, geographic and economic (CAGE) – distance between countries and its influence on the strategy of international subsidiaries.

Design/methodology/approach
This study applies the transaction cost and behavioural theory and presents an exploratory and qualitative methodology approach through six semi-structured in-depth interviews to evaluate managers’ perceptions of distance between countries.

Findings
The research findings show that cultural and economic distances indeed have a major influence on subsidiary strategy and a smaller impact of administrative and geographic dimensions, which results into forced changes on the marketing-mix, i.e. product, price, design and brand, as well as on the level of autonomy granted to foreign subsidiaries.

Research limitations/implications
The limitation is related to the home country and the entry mode of foreign direct investment. The findings presented here reflect the nature and behaviour of Portuguese companies with subsidiaries.

Practical implications
The research provides recommendations for managers to be aware of the influence of more than one dimension of distance between countries to improve their decision-making of standardisation-adaptation strategy for foreign subsidiaries. Furthermore, the study stresses that managers’ perceptions may lead to the conclusion that proximity and knowledge of foreign markets does not make international business easier.

Originality/value
This empirical research not only tests the transaction cost theory and behavioural theory on managers’ decisions to invest abroad but also promotes organisational changes to achieve the suitable strategy for international subsidiaries. The study contributes to the area of international business by positing six research propositions concerning distance between countries to be tested in future studies.
Phycocyanobilin reduces brain injury after endothelin‐1‐ induced focal cerebral ischaemia
Authors: Pavón‐Fuentes Nancy , Marín‐Prida Javier , Llópiz‐Arzuaga Alexey , Falcón‐Cama Viviana , Campos‐Mojena Rosario , Cervantes‐Llanos Majel , Piniella‐Matamoros Beatriz , Pentón‐Arias Eduardo , Pentón‐Rol Giselle 
Published: November 2019

AbstractPharmacological therapies for interrupting biochemical events of the ischaemic cascade and protecting against stroke in humans are as yet unavailable. Up to now, the neuroprotective activity in cerebral ischaemia of phycocyanobilin (PCB), a tetrapyrrolic natural antioxidant, has not been fully examined. Here, we evaluated if PCB protects PC12 neuronal cells against oxygen and glucose deprivation plus reperfusion, and its protective effects in a rat model of endothelin‐1‐induced focal brain ischaemia. PCB was purified from the cyanobacteria Spirulina platensis and characterized by spectrophotometric, liquid and gas chromatography and mass spectrometry techniques. In Wistar rats, PCB at 50, 100 and 200 μg/kg or phosphate‐buffered saline (vehicle) was administered intraperitoneally at equal subdoses in a therapeutic schedule (30 minutes, 1, 3 and 6 hours after the surgery). Brain expression of myelin basic protein (MBP) and the enzyme CNPase was determined by immunoelectron microscopy. PCB was obtained with high purity (>95%) and the absence of solvent contaminants and was able to ameliorate PC12 cell ischaemic injury. PCB treatment significantly decreased brain infarct volume, limited the exploratory behaviour impairment and preserved viable cortical neurons in ischaemic rats in a dose‐dependent manner, compared to the vehicle group. Furthermore, PCB at high doses restored the MBP and CNPase expression levels in ischaemic rats. An improved PCB purification method from its natural source is reported, obtaining PCB that is suitable for pharmacological trials showing neuroprotective effects against experimental ischaemic stroke. Therefore, PCB could be a therapeutic pharmacological alternative for ischaemic stroke patients.
Enabling strategies and impeding factors to urban resilience implementation: A scoping review
Authors: Therrien Marie‐Christine , Usher Susan , Matyas David 
Published: November 2019

AbstractDespite growing interest in urban resilience, there is a significant gap between discourse and the capacity to develop resilience in practice. This scoping review assembles and shares evidence and insights from empirical studies of attempts to implement urban resilience published between 2005 and 2017. More precisely, it seeks to identify enabling strategies, impeding factors and trade‐offs in the implementation of urban resilience. Findings are presented along the dimensions of urban resilience detailed in the City Resilience Framework (ARUP/Rockefeller Foundation): Health and Wellbeing, Economy and Society, Infrastructure and Environment, and Leadership and Strategy (which we present as a cross‐cutting theme). While some enabling and impeding factors in implementation are associated with a specific dimension, others are common to all three. Across dimensions, we find that transparent, inclusive and supportive governance reduces the risk of negative impact that resilience implementation will have on communities. Conflicting priorities of managing risk and meeting short‐term needs are found to diminish the potential for transformative resilience action. Integrating risk into planning appears as a promising strategy in all dimensions of resilience. Trade‐offs are found in resilience implementation, and range from adverse effects associated with infrastructure to power imbalances when the power to implement resilience privileges one system level over another.
The housing price premium associated with charter schools
Authors: Beracha Eli , Hardin William G. 
Published: November 2019

AbstractThe existing literature documents a clear relation between public school quality and a residential real estate price premium. The literature on whether charter school availability and quality are associated with a price premium, however, is surprisingly thin. After controlling for public school quality, we provide evidence that residential real estate price premiums are associated with charter school availability and quality. The price premium is smaller than that of quality public schools, but is economically meaningful when the quality of charter schools exceeds the quality of public schools. The price premium associated with charter schools is more prominent in areas where a large percentage of the population is between the ages of 6 and 18 and for family‐oriented housing types. We also show that the premium associated with quality charter schools varies with school type and is highest for high schools. The findings contribute to the literature on school quality with policy implications relating to school choice options such as charter schools and vouchers.