bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific gut microbiome members are associated with distinct immune markers in allogeneic hematopoietic stem cell transplantation
Authors: Masche Anna Cäcilia , Kielsen Katrine , Cilieborg Malene Skovsted , Lund Ole , Holmes Susan , Aarestrup Frank M. , Müller Klaus Gottlob , Pamp Sünje Johanna 
Published: March 2019

AbstractBackgroundIncreasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation, (HSCT), i.e. a replacement of the cellular components of the patients’ immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g. at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly.ResultsIn two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) High concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances ofLactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such asRuminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such asEnterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state.ConclusionsWe identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.
Metabolite sequestration enables rapid recovery from fatty acid depletion in Escherichia coli
Authors: Hartline Christopher J. , Mannan Ahmad A. , Liu Di , Zhang Fuzhong , Oyarzún Diego A. 
Published: March 2019

AbstractMicrobes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival in the new nutritional condition. Yet little is known about the regulatory strategies that microbes employ to accelerate pathway recovery in response to nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli, here we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of mathematical modelling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrient. We constructed strains with re-wired transcriptional regulatory architectures that highlight the metabolic benefits of negative autoregulation over constitutive and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic adaptations, as well as guiding the design of gene circuitry for synthetic biology and metabolic engineering.
Heroin Type, Injecting Behavior, and HIV Transmission. A Simulation Model of HIV Incidence and Prevalence
Authors: Bobashev Georgiy V. , Mars Sarah , Murphy Nicholas , Dreisbach Clinton , Zule William , Ciccarone Daniel 
Published: March 2019

ABSTRACTBackground and AimsUsing mathematical modeling to illustrate and predict how different heroin source-forms: “black tar” (BTH) and powder heroin (PH) can affect HIV transmission in the context of contrasting injecting practices. By quantifying HIV risk by these two heroin source-types we show how each affects the incidence and prevalence of HIV over time. From 1997 to 2010 PH reaching the United States was manufactured overwhelmingly by Colombian suppliers and distributed in the eastern states of the United States. Recently Mexican cartels that supply the western U.S. states have started to produce PH too, replacing Colombian distribution to the east. This raises the possibility that BTH in the western U.S. may be replaced by PH in the future.DesignWe used an agent-based model to evaluate the impact of use of different heroin formulations in high- and low-risk injecting drug user populations who use different types of syringes (high vs. low dead space) and injecting practices. We obtained model parameters from peer-reviewed publications and ethnographic research.ResultsHeating of BTH, additional syringe rinsing, and subcutaneous injection can substantially decrease the risk of HIV transmission. Simulation analysis shows that HIV transmission risk may be strongly affected by the type of heroin used. We reproduced historic differences in HIV prevalence and incidence. The protective effect of BTH is much stronger in high-risk compared with low-risk populations. Simulation of future outbreaks show that when PH replaces BTH we expect a long-term overall increase in HIV prevalence. In a population of injectors with mixed low- and high-risk clusters we find that local HIV outbreaks can occur even when the overall prevalence and incidence are low. The results are dependent on evidence-supported assumptions.ConclusionsThe results support harm-reduction measures focused on a reduction in syringe sharing and promoting protective measures of syringe rinsing and drug solution heating.
Bioactivity-guided isolation of rosmarinic acid as a principle bioactive compound from the butanol extract of Isodon rugosus against pea aphid, Acyrthosiphon pisum
Authors: Khan Saira , Tizi Taning Clauvis Nji , Bonneure Elias , Mangelinckx Sven , Smagghe Guy , Ahmad Raza , Fatima Nighat , Asif Muhammad , Shah Mohammad Maroof 
Published: March 2019

AbstractAphids are agricultural pest insects that transmit viruses and cause feeding damage on a global scale. Current pest control involving the excessive use of synthetic insecticides over decades has led to multiple forms of aphid resistance to most classes of insecticides. In nature, plants produce secondary metabolites during their interaction with insects and these metabolites can act as toxicants, antifeedants, anti-oviposition agents and deterrents towards the insects. In a previous study, we demonstrated that the butanol fraction from a crude methanolic extract of an important plant species, Isodon rugosus showed strong insecticidal activity against the pea aphid, Acyrthosiphon pisum. It was however not known as which compound was responsible for such activity. To further explore this finding, current study aimed to exploit a bioactivity-guided strategy to isolate and identify the active compound in the butanol fraction of I. rugosus. As such, reversed-phase flash chromatography, acidic extraction and different spectroscopic techniques were used to isolate and identify the new compound, rosmarinic acid as the bioactive compound in I. rugosus. Insecticidal activity of rosmarinic acid was carried out using standard protocols on A. pisum. The data was analyzed using qualitative and quantitative statistical approaches. Considering that a very low concentration of this compound (LC90 = 5.4 ppm) causes significant mortality in A. pisum within 24 h, rosmarinic acid could be exploited as a potent insecticide against this important pest insect. Furthermore, I. rugosus is already used for medicinal purposes and rosmarinic acid is known to reduce genotoxic effects induced by chemicals, hence it is expected to be safer compared to the current conventional pesticides. While this study highlights the potential of I. rugosus as a possible biopesticide source against A. pisum, it also provides the basis for further exploration and development of formulations for effective field application.
Integration of pathway, cellular and genetic context reveals principles of synthetic lethality that affect reproducibility
Authors: Ku Angel A. , Kongara Sameera , Hu Hsien-Ming , Zhao Xin , Wu Di , McCormick Frank , Balmain Allan , Bandyopadhyay Sourav 
Published: March 2019

ABSTRACTSynthetic lethal screens have the potential to identify new vulnerabilities incurred by specific cancer mutations but have been hindered by lack of agreement between studies. Using KRAS as a model, we identified that published synthetic lethal screens significantly overlap at the pathway rather than gene level. Analysis of pathways encoded as protein networks identified synthetic lethal candidates that were more reproducible than those previously reported. Lack of overlap likely stems from biological rather than technical limitations as most synthetic lethal phenotypes were strongly modulated by changes in cellular conditions or genetic context, the latter determined using a pairwise genetic interaction map that identified numerous interactions that suppress synthetic lethal effects. Accounting for pathway, cellular and genetic context nominates a DNA repair dependency in KRAS-mutant cells, mediated by a network containing BRCA1. We provide evidence for why most reported synthetic lethals are not reproducible which is addressable using a multi-faceted testing framework.STATEMENT OF SIGNIFICANCESynthetic lethal screens have the power to identify new targets in cancer, although have thus far come up short of expectation. We use computational and experimental approaches to delineate principles for identifying robust synthetic lethal targets that could aid in the development of effective new therapeutic strategies for genetically defined cancers.
Changepoint detection versus reinforcement learning: Separable neural substrates approximate different forms of Bayesian inference
Authors: Pauli Wolfgang M. , Jones Matt 
Published: March 2019

AbstractAdaptive behavior in even the simplest decision-making tasks requires predicting future events in an environment that is generally nonstationary. As an inductive problem, this prediction requires a commitment to the statistical process underlying environmental change. This challenge can be formalized in a Bayesian framework as a question of choosing a generative model for the task dynamics. Previous learning models assume, implicitly or explicitly, that nonstationarity follows either a continuous diffusion process or a discrete changepoint process. Each approach is slow to adapt when its assumptions are violated. A new mixture of Bayesian experts framework proposes separable brain systems approximating inference under different assumptions regarding the statistical structure of the environment. This model explains data from a laboratory foraging task, in which rats experienced a change in reward contingencies after pharmacological disruption of dorsolateral (DLS) or dorsomedial striatum (DMS). The data and model suggest DLS learns under a diffusion prior whereas DMS learns under a changepoint prior. The combination of these two systems offers a new explanation for how the brain handles inference in an uncertain environment.One Sentence SummaryAdaptive foraging behavior can be explained by separable brain systems approximating Bayesian inference under different assumptions about dynamics of the environment.
Effects of carbon nanotubes and derivatives of graphene oxide on soil bacterial diversity
Authors: Forstner Christian , Orton Thomas G. , Wang Peng , Kopittke Peter M. , Dennis Paul G. 
Published: March 2019

AbstractCarbon nanotubes (CNTs), reduced graphene oxide (rGO) and ammonia-functionalized graphene oxide (aGO), are nanomaterials that possess varied and useful properties. However, following their use, their release into the environment is inevitable. While CNTs have been shown to influence soil bacterial diversity, albeit at very high concentration, the effects of rGO have only been examined using pure bacterial cultures, and those of aGO are unknown. Here, we investigated the effects of CNTs, rGO and aGO, at three time points (7, 14 and 30 days), and over a range of concentrations (1 ng, 1 µg and 1 mg kg dry soil-1), on soil bacterial diversity using 16S rRNA amplicon sequencing. Graphite was included to facilitate comparisons with a similar and naturally occurring carbon material, while the inclusion of GO allowed the effects of GO modification to be isolated. Bacterial community composition, but not alpha diversity, was altered by all treatments except the low GO, low rGO and high aGO treatments on day 14 only. In all cases, the nanomaterials led to shifts in community composition that were of similar magnitude to those induced by graphite and GO, albeit with differences in the taxa affected. Our study highlights that nanocarbon materials can induce changes in soil bacterial diversity, even at doses that are environmentally realistic.
Animal evolution coincides with a novel degree of freedom in exocytic transport processes
Authors: Kollmar Martin , Welz Tobias , Straub Felix , Alzahofi Noura , Hatje Klas , Briggs Deborah A. , Samol-Wolf Annette , Burkhardt Pawel , Hume Alistair , Kerkhoff Eugen 
Published: March 2019

AbstractExocytic transport of transmembrane receptors and secreted ligands provides the basis for cellular communication in animals. The RAB8/RAB3/RAB27 trafficking regulators function in transport processes towards the cell membrane. The small G-proteins recruit a diversity of effectors that mediate transport along microtubule and actin tracks, as well as membrane tethering and fusion. SPIRE actin nucleators organise local actin networks at exocytic vesicle membranes. By complex formation with class-5 myosins, vesicle transport track generation and motor protein activation are coordinated. Our phylogenetic analysis traced the onset of SPIRE function back to the origin of the Holozoa. We have identified SPIRE in the closest unicellular relatives of animals, the choanoflagellates, and the more distantly related ichthyosporeans. The discovery of a SPIRE-like protein encoding a KIND and tandem-WH2 domains in the amoebozoanPhysarum polycephalumsuggests that the SPIRE-type actin nucleation mechanism originated even earlier. Choanoflagellate SPIRE interacts with RAB8, the sole choanoflagellate representative of the metazoan RAB8/RAB3/RAB27 family. Major interactions including MYO5, FMN-subgroup formins and vesicle membranes are conserved between the choanoflagellate and mammalian SPIRE proteins and the choanoflagellateMonosiga brevicollisSPIRE protein can rescue mouse SPIRE1/2 function in melanosome transport. Genome duplications generated two mammalianSPIREgenes (SPIRE1andSPIRE2) and allowed for the separation of SPIRE protein function in terms of tissue expression and RAB GTPase binding. SPIRE1 is highest expressed in the nervous system and interacts with RAB27 and RAB8. SPIRE2 shows high expression in the digestive tract and specifically interacts with RAB8. We propose that at the dawn of the animal kingdom a new transport mechanism came into existence, which bridges microtubule tracks, detached vesicles and the cellular actin cytoskeleton by organising actin/myosin forces directly at exocytic vesicle membranes. The new degree of freedom in transport may reflect the increased demands of the sophisticated cellular communications in animals.
Family aggregation analysis reveals a heritable background of equine grass sickness (dysautonomia)
Authors: Vincze Boglárka , Varga Márta , Gáspárdy András , Kutasi Orsolya , Zenke Petra , Szenci Ottó , Baska Ferenc , Bartels Alan , Spisák Sándor , Solymosi Norbert 
Published: March 2019

AbstractEquine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since it’s first description over a hundred years ago, several factors including phenotypic, environmental, management, climate, and intestinal microbiome) have been associated with increased risk of dysautonomia. But despite the extensive research on dysautonomia, it’s causative factors have yet been identified. A retrospective pedigree and phenotype based genetic epidemiological study was performed to analyze the associations of disease occurrence and the kinship in a Hungarian large scale stud. The pedigree data set containing 1233 horses with 49 affected animals was used in the analysis. The first finding was that among the descendants of some stallions the proportion of affected animals are unexpectedly high, with a maximum of 25% of a stallions descendants affected. Animals with affected siblings have higher odds to be a case (OR: 1.27, 95% CI: 1.01-1.57, p=0.033). Among males in the affected population the odds of dysautonomia is higher than in females (OR: 1.76, 95% CI: 0.95-3.29, p=0.057). Significant familial clustering was observed among the affected animals (GIF p=0.001). Further subgroups were identified with significant (p<0.001) aggregation among close relatives using kinship-based methods. Our analysis of the data and the observed higher disease frequency in males suggests that dysautonomia may have X-linked recessive inheritance as a causal factor. This is the first study providing ancestry data and suggesting a genetic contribution to the likely multifactorial causes of the disease.
Quantitative Colour Pattern Analysis (QCPA): A Comprehensive Framework for the Analysis of Colour Patterns in Nature
Authors: van den Berg Cedric P. , Troscianko Jolyon , Endler John A. , Marshall N. Justin , Cheney Karen L. 
Published: March 2019

AbstractTo understand the function of colour signals in nature, we require robust quantitative analytical frameworks to enable us to estimate how animal and plant colour patterns appear against their natural background as viewed by ecologically relevant species. Due to the quantitative limitations of existing methods, colour and pattern are rarely analysed in conjunction with one another, despite a large body of literature and decades of research on the importance of spatiochromatic colour pattern analyses. Furthermore, key physiological limitations of animal visual systems such as spatial acuity, spectral sensitivities, photoreceptor abundances and receptor noise levels are rarely considered together in colour pattern analyses.Here, we present a novel analytical framework, called the ‘Quantitative Colour Pattern Analysis’ (QCPA). We have overcome many quantitative and qualitative limitations of existing colour pattern analyses by combining calibrated digital photography and visual modelling. We have integrated and updated existing spatiochromatic colour pattern analyses, including adjacency, visual contrast and boundary strength analysis, to be implemented using calibrated digital photography through the ‘Multispectral Image Analysis and Calibration’ (MICA) Toolbox.This combination of calibrated photography and spatiochromatic colour pattern analyses is enabled by the inclusion of psychophysical colour and luminance discrimination thresholds for image segmentation, which we call ‘Receptor Noise Limited Clustering’, used here for the first time. Furthermore, QCPA provides a novel psycho-physiological approach to the modelling of spatial acuity using convolution in the spatial or frequency domains, followed by ‘Receptor Noise Limited Ranked Filtering’ to eliminate intermediate edge artefacts and recover sharp boundaries following smoothing. We also present a new type of colour pattern analysis, the ‘Local Edge Intensity Analysis’ (LEIA) as well as a range of novel psycho-physiological approaches to the visualisation of spatiochromatic data.QCPA combines novel and existing pattern analysis frameworks into what we hope is a unified, user-friendly, free and open source toolbox and introduce a range of novel analytical and data-visualisation approaches. These analyses and tools have been seamlessly integrated into the MICA toolbox providing a dynamic and user-friendly workflow.QCPA is a framework for the empirical investigation of key theories underlying the design, function and evolution of colour patterns in nature. We believe that it is compatible with, but more thorough than, other existing colour pattern analyses.
Does innovation capabilities affect the new service innovation success among Pakistani cellular companies?
Authors: Kiani Malkah Noor , Mustafa Syed Hussain , Ahmad Mehboob 
Published: March 2019

PurposeIn today’s Pakistan, the emergence of new forms of business in collaboration with the mobile service providers is bringing a big difference, not only in every walk of life but also in digital economy of the country. Therefore, the purpose of this paper is to explore what are the factors that determine the success rate of new innovative services in cultural context of mobile service providers of Pakistan.Design/methodology/approachData have been collected from 397 employees of cellular firms of Pakistan by using the simple random sampling strategy. The gathered data were analyzed by using the regression-based process approach of Hayes and Preacher (2014).FindingsThe results indicated that innovation capabilities and service innovation have significant positive effect on the short-term, long-term and indirect success of the service innovation. It was also found that the service innovation mediates the relationship among the capabilities to innovate and service innovation success rate. The findings of this research work are beneficial for the practitioners of cellular firms of Pakistan.Originality/valueThe value of this research work is evident from the fact that this research work attempts to address some identified gaps of existing body of literature. This research work provides some key insights for practitioners and also discusses the new avenues for future researches.