bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking trends in monarch abundances over the 20thcentury is currently impossible using museum records: a response to Boyle et al. (2019)
Authors: Ries Leslie , Zipkin Elise F. , Guralnick Rob P. 
Published: March 2019

AbstractThe onslaught of opportunistic data offers new opportunities to examine biodiversity patterns at large scales. However, the techniques for tracking abundance trends with such data are new and require careful consideration to ensure that variations in sampling effort do not lead to biased estimates. The analysis by Boyle et al. (2019) showing a mid-century increase in monarch abundance followed by a decrease starting in the 1960s used an inappropriate correction with respect to three dimensions of sampling effort: taxonomy, place, and time. When the data presentenced by Boyle et al. (2019) are corrected to account for biases in the collection process, the results of their analyses do not hold. The paucity of data that remain after accounting for spatial and temporal biases suggests that analyses of monarch trends back to the beginning of the 20thare currently not possible. Continued digitization of museum records is needed to provide a firm data basis to estimate population trends.
Diverse commensal E. coli clones and plasmids disseminate antimicrobial resistance genes in domestic animals and children in a semi-rural community in Ecuador
Authors: Salinas Liseth , Cárdenas Paúl , Johnson Timothy J. , Vasco Karla , Graham Jay , Trueba Gabriel 
Published: March 2019

ABSTRACTThe increased prevalence of antimicrobial resistance (AMR) among Enterobacteriaceae has had major clinical and economic impacts in human medicine. Many of the multi-drug resistant (MDR) Enterobacteriaceae found in humans are community-acquired and linked to food animals (i.e. livestock raised for meat and dairy products). In this study, we examined whether numerically dominant, commensal Escherichia coli strains from humans (n=63 isolates) and domestic animals (n=174 isolates) in the same community and with matching phenotypic AMR patterns, were clonally related or shared the same plasmids. We identified 25 multi-drug resistant isolates (i.e. resistant to 3 or more antimicrobial classes) that shared identical phenotypic resistance patterns. We then investigated the diversity of E. coli clones, AMR genes and plasmids carrying the AMR genes using conjugation, replicon typing and whole genome sequencing. None of the MDR E. coli isolates (from children and domestic animals) analyzed were clonal. While the majority of isolates shared the same antimicrobial resistance genes and replicons, DNA sequencing indicated that these genes and replicons were found on different plasmid structures. Our findings suggest that nonclonal resistance gene dissemination is common in this community and that diverse plasmids carrying AMR genes presents a significant challenge for understanding the movement of AMR in a community.IMPORTANCEEven though Escherichia coli strains may share nearly identical AMR profiles, AMR genes, and overlap in space and time, the diversity of clones and plasmids challenges to research that aims to identify sources of AMR. Horizontal gene transfer appears to play a much larger role than clonal expansion in the spread of AMR in the community.
Environmental chemical diethylhexyl phthalate alters intestinal microbiota community structure and metabolite profile in mice
Authors: Lei Ming , Menon Rani , Manteiga Sara , Alden Nicholas , Hunt Carrie , Alaniz Robert C. , Lee Kyongbum , Jayaraman Arul 
Published: March 2019

AbstractExposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis, and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance ofLachnoclostridum, while decreasingAkkermansia, Odoribacter, andClostridium sensu stricto. Addition of DEHP toin vitrocultured cecal microbiota increased the abundance ofAlistipes, Paenibacillus, andLachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production ofp-cresol, while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources ofp-cresol areClostridiumspecies. Our results suggest that DEHP can directly modify the microbiota to affect production of bacterial metabolites linked with neurodevelopmental disorders.ImportanceSeveral previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders, and correlated these disorders with microbiota dysbiosis, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Further, we use a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.
Coxiella burnetii epitope-specific T-cell responses in chronic Q fever patients
Authors: Scholzen Anja , Richard Guilhem , Moise Leonard , Hartman Eva , Bleeker-Rovers Chantal P. , Reeves Patrick M. , Paul Susan Raju , Martin William D. , Groot Anne S. De , Poznansky Mark C. , Sluder Ann E. , Garritsen Anja 
Published: March 2019

AbstractInfection with Coxiella burnetii, the causative agent of Q fever, can result in life-threatening persistent infection. Reactogenicity hinders worldwide implementation of the only licensed human Q fever vaccine. We previously demonstrated long-lived immunoreactivity in individuals with past symptomatic and asymptomatic Coxiella infection (convalescents) to promiscuous HLA-class II C. burnetii epitopes, providing the basis for a novel T-cell-targeted subunit vaccine. Here we investigated in a cohort of 22 individuals with persistent infection (chronic Q fever) whether they recognize the same set of epitopes, or distinct epitopes that could be candidates for a therapeutic vaccine or aid in the diagnosis of persistent infection.Individuals with chronic Q fever showed strong class II epitope-specific cultured ELISpot responses largely overlapping with the peptide repertoire identified previously for convalescents. Five additional peptides were recognized more frequently by chronic subjects, but there was no combination of epitopes uniquely recognized by or non-reactive in chronic Q fever subjects. Consistent with more recent/prolonged exposure, we found, however, stronger direct ex vivo responses to whole-cell C. burnetii and individual peptides in direct ELISpot than in convalescents.In conclusion, we have validated and expanded a previously published set candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in the context of chronic Q fever patients and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrate that individuals treated for chronic Q fever mount a broader ex vivo response to class II epitopes than convalescents, which could be explored for diagnostic purposes.
Septate junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior inDrosophila
Authors: Izumi Yasushi , Furuse Kyoko , Furuse Mikio 
Published: March 2019

AbstractSmooth septate junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in theDrosophilamidgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in theDrosophilaadult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, suppressed the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in theDrosophilaadult midgut.Summary statementDepletion of smooth septate junction-associated proteins from enterocytes in theDrosophilaadult midgut results in intestinal hypertrophy accompanied by accumulation of morphologically aberrant enterocytes and increased stem cell proliferation.
Individual variation in the attribution of incentive salience to social cues
Authors: Fitzpatrick Christopher J. , Morrow Jonathan D. 
Published: March 2019

AbstractResearch on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals as well as drug relapse and craving in humans. The influence of peers and other social cues on drug-seeking has garnered more attention recently, but few studies have investigated the ability of social cues to gain incentive-motivational value. In the present study, a Pavlovian conditioned approach procedure was used to identify rats that are more (sign-trackers) or less (goal-trackers) prone to attribute incentive salience to food reward cues. A novel procedure then employed social ‘peers’ to compare the tendency of sign-trackers and goal-trackers to attribute incentive salience to social reward cues. Social behavior of sign-trackers and goal-trackers was also compared using social interaction and choice tests. Finally, basal levels of plasma oxytocin were measured in sign-trackers and goal-trackers, because oxytocin is known to modulate the mesolimbic reward system and social behavior. Compared to goal-trackers, sign-trackers attributed more incentive salience to social cues and exhibited more prosocial behaviors. No group differences were observed in baseline plasma oxytocin levels. Taken together, these experiments demonstrate a concordance of individual variation in social behavior, the attribution of incentive salience to social cues following peer interaction, and attribution of incentive salience to food cues. This general tendency to attribute motivational value to reward cues has important implications for the pathophysiology of addiction and other disorders of reward learning.
Comparison of real-time PCR and droplet digital PCR for the detection of Xylella fastidiosa in plants
Authors: Dupas Enora , Legendre Bruno , Olivier Valérie , Poliakoff Françoise , Manceau Charles , Cunty Amandine 
Published: March 2019

AbstractXylella fastidiosa (Xf) is a quarantine plant pathogen bacterium originating from the Americas and that has emerged in Europe in 2013. Xf can be detected directly on plant macerate using molecular methods such as real-time PCR, which is a sensitive technique. However, some plants may contain components that can act as PCR reaction inhibitors, which can lead to false negative results or an underestimation of the bacterial concentration present in the analyzed plant sample. Droplet digital PCR (ddPCR) is an innovative tool based on the partitioning of the PCR reagents and the DNA sample into thousands of droplets, allowing the quantification of the absolute number of target DNA molecules present in a reaction mixture, or an increase of the detection sensitivity. In this study, a real-time PCR protocol, already used for Xf detection in the framework of official surveys in the European Union, was transferred and optimized for Xf detection using ddPCR. This new assay was evaluated and compared to the initial real-time PCR on five plant matrices artificially inoculated and on naturally infected plants. In our conditions, this new ddPCR enabled the detection of Xf on all artificially inoculated plant macerates with a similar limit of detection, or a slight benefit for Quercus ilex. Moreover, ddPCR improved diagnostic sensitivity as it enabled detection of Xf in samples of Polygala myrtifolia or Q. ilex that were categorized as negative or close to the limit of detection using the real-time PCR. Here, we report for the first time a ddPCR assay for the detection of the bacterium Xf.
Local cortical desynchronization and pupil-linked arousal differentially shape brain states for optimal sensory performance
Authors: Waschke Leonhard , Tune Sarah , Obleser Jonas 
Published: March 2019

AbstractInstantaneous brain states have consequences for our sensation, perception, and behaviour. Fluctuations in arousal and neural desynchronization likely pose perceptually relevant states. However, their relationship and their relative impact on perception is unclear. We here show that, at the single-trial level in humans, local desynchronization in sensory cortex (expressed as time-series entropy) versus pupil-linked arousal differentially impact perceptual processing. While we recorded electroencephalography (EEG) and pupillometry data, stimuli of a demanding auditory discrimination task were presented into states of high or low desynchronization of auditory cortex via a real-time closed-loop setup. Desynchronization and arousal distinctly influenced stimulus-evoked activity and shaped behaviour displaying an inverted u-shaped relationship: States of intermediate desynchronization elicited minimal response bias and fastest responses, while states of intermediate arousal gave rise to highest response sensitivity. Our results speak to a model in which independent states of local desynchronization and global arousal jointly optimise sensory processing and performance.
A generic deviance detection principle for cortical On/Off responses, omission response, and mismatch negativity
Authors: Chien Shih-Cheng , Maess Burkhard , Knösche Thomas R. 
Published: March 2019

AbstractNeural responses to sudden changes can be observed in many parts of the sensory pathways at different organizational levels. For example, deviants that violate regularity at various levels of abstraction can be observed as simple On/Off responses of individual neurons or as cumulative responses of neural populations. The cortical deviance-related responses supporting different functionalities (e.g. gap detection, chunking, etc.) seem unlikely to arise from different function-specific neural circuits, given the relatively uniform and self-similar wiring patterns across cortical areas and spatial scales. Additionally, reciprocal wiring patterns (with heterogeneous combinations of excitatory and inhibitory connections) in the cortex naturally speak in favor of a generic deviance detection principle. Based on this concept, we propose a network model consisting of reciprocally coupled neural masses as a blueprint of a universal change detector. Simulation examples reproduce properties of cortical deviance-related responses including the On/Off responses, the omitted-stimulus response (OSR), and the mismatch negativity (MMN). We propose that the emergence of change detectors relies on the involvement of disinhibition. The analysis on network connection settings further suggests a supportive effect of synaptic adaptation and a destructive effect of N-methyl-D-aspartate receptor (NMDA-r) antagonists on change detection. We conclude that the nature of cortical reciprocal wirings gives rise to a whole range of local change detectors supporting the notion of a generic deviance detection principle. Several testable predictions are provided based on the network model. Notably, we predict that the NMDA-r antagonists would generally dampen the cortical Off response, the cortical OSR, and the MMN.
DOCK2 sets the threshold for entry into the virtual memory CD8+T cell compartment by negatively regulating tonic TCR triggering
Authors: Demissie Ezana , Mahajan Vinay S , Alsufyani Faisal , Kumari Sudha , Yuen Grace J , Viswanadham Vinayak , Tran Johnson Q. , Moon James J. , Irvine Darrell J , Pillai Shiv 
Published: March 2019

AbstractThe control of cytoskeletal dynamics by Dedicator of cytokinesis 2 (DOCK2), a hematopoietic cell-specific actin effector protein, has been implicated in TCR signaling and T cell migration. Biallelic mutations inDock2have been identified in patients with a recessive form of combined immunodeficiency with defects in T, B and NK cell activation. Surprisingly, we show here that certain immune functions of CD8+T cells are enhanced in the absence of DOCK2.Dock2-deficient mice have a pronounced expansion of their memory T cell compartment. Bone marrow chimera and adoptive transfer studies indicate that these memory T cells develop in a cell-intrinsic manner following thymic egress. Transcriptional profiling, TCR repertoire analyses and cell surface marker expression indicate thatDock2-deficient naive CD8+T cells directly convert into virtual memory cells without clonal effector T cell expansion. This direct conversion to memory is associated with a selective increase in TCR sensitivity to selfpeptide MHCin vivoand an enhanced response to weak agonist peptidesex vivo. In contrast, the response to strong agonist peptides remains unaltered inDock2-deficient T cells. Collectively, these findings suggest that the regulation of the actin dynamics by DOCK2 enhances the threshold for entry into the virtual memory compartment by negatively regulating tonic TCR triggering in response to weak agonists.
Training propulsion: Locomotor adaptation to accelerations of the trailing limb
Authors: Farrens Andria J. , Marbaker Rachel , Lilley Maria , Sergi Fabrizio 
Published: March 2019

AbstractMany stroke survivors suffer from hemiparesis, a condition that results in impaired walking ability. Walking ability is commonly assessed by walking speed, which is dependent on propulsive force both in healthy and stroke populations. Propulsive force is determined by two factors: ankle moment and the posture of the trailing limb during push-off. Recent work has used robotic assistance strategies to modulate propulsive force with some success. However, robotic strategies are limited by their high cost and the technical difficulty of fitting and operating robotic devices with stroke survivors in a clinical setting.We present a new paradigm for goal-oriented gait training that utilizes a split belt treadmill to train both components of propulsive force generation, achieved by accelerating the treadmill belt of the trailing limb during push off. Belt accelerations require subjects to produce greater propulsive force to maintain their position on the treadmill and increases trailing limb angle through increased velocity of the accelerated limb.We hypothesized that accelerations would cause locomotor adaptation that would result in measurable after effects in the form of increased propulsive force generation. We tested our protocol on healthy subjects at two levels of belt accelerations. Our results show that 79% of subjects significantly increased propulsive force generation, and that larger accelerations translated to larger, more persistent behavioral gains.
A genetic screen using theDrosophila melanogasterTRiP RNAi collection to identify metabolic enzymes required for eye development
Authors: Pletcher Rose C. , Hardman Sara L. , Intagliata Sydney F. , Lawson Rachael L. , Page Aumunique , Tennessen Jason M. 
Published: March 2019

ABSTRACTThe metabolic enzymes that compose glycolysis, the citric acid cycle, and other pathways within central carbon metabolism have emerged as key regulators of animal development. These enzymes not only generate the energy and biosynthetic precursors required to support cell proliferation and differentiation, but also moonlight as regulators of transcription, translation, and signal transduction. Many of the genes associated with animal metabolism, however, have never been analyzed in a developmental context, thus highlighting how little is known about the intersection of metabolism and development. Here we address this deficiency by using theDrosophilaTRiP RNAi collection to disrupt the expression of over 1,100 metabolism-associated genes within cells of the eye imaginal disc. Our screen not only confirmed previous observations that oxidative phosphorylation serves a critical role in the developing eye, but also implicated a host of other metabolic enzymes in the growth and differentiation of this organ. Notably, our analysis revealed a requirement for glutamine and glutamate metabolic processes in eye development, thereby revealing a role of these amino acids in promotingDrosophilatissue growth. Overall, our analysis highlights how theDrosophilaeye can serve as a powerful tool for dissecting the relationship between development and metabolism.
Combining gene network, metabolic, and leaf-level models show means to future-proof soybean photosynthesis under rising CO2
Authors: Kannan Kavya , Wang Yu , Lang Meagan , Challa Ghana S. , Long Stephen P. , Marshall-Colon Amy 
Published: March 2019

ABSTRACTGlobal population increase coupled with rising urbanization underlies the predicted need for 60% more food by 2050, but produced on the same amount of land as today. Improving photosynthetic efficiency is a largely untapped approach to addressing this problem. Here, we scale modeling processes from gene expression through photosynthetic metabolism to predict leaf physiology in evaluating acclimation of photosynthesis to rising [CO2]. Model integration with the yggdrasil interface enabled asynchronous message passing between models. The multiscale model of soybean photosynthesis calibrated to physiological measures at ambient [CO2] successfully predicted the acclimatory changes in the photosynthetic apparatus that were observed at 550 ppm [CO2] in the field. We hypothesized that genetic alteration is necessary to achieve optimal photosynthetic efficiency under global change. Flux control analysis in the metabolic system under elevated [CO2] identified enzymes requiring the greatest change to adapt optimally to the new conditions. This predicted that Rubisco was less limiting under elevated [CO2] and should be down-regulated allowing re-allocation of resource to enzymes controlling the rate of regeneration of ribulose-1:5 bisphosphate (RubP). By linking the GRN through protein concentration to the metabolic model it was possible to identify transcription factors (TF) that matched the up- and down-regulation of genes needed to improve photosynthesis. Most striking was TF GmGATA2, which down-regulated genes for Rubisco synthesis while up-regulating key genes controlling RubP regeneration and starch synthesis. The changes predicted for this TF most closely matched the physiological ideotype that the modeling predicted as optimal for the future elevated [CO2] world.