bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the fundamental thermal niche of crop pests and diseases in a changing world: a case study on citrus greening
Authors: Taylor Rachel A. , Ryan Sadie J. , Lippi Catherine A. , Hall David G. , Narouei-Khandan Hossein A. , Rohr Jason R. , Johnson Leah R. 
Published: November 2018

AbstractPredicting where crop pests and diseases can occur, both now and in the future under different climate change scenarios, is a major challenge for crop management. One solution is to estimate the fundamental thermal niche of the pest/disease to indicate where establishment is possible. Here we develop methods for estimating and displaying the fundamental thermal niche of pests and pathogens and apply these methods to Huanglongbing (HLB), a vector-borne disease that is currently threatening the citrus industry worldwide.We derive a suitability metric based on a mathematical model of HLB transmission between tree hosts and its vectorDiaphorina citri, and incorporate the effect of temperature on vector traits using data from laboratory experiments performed at different temperatures. We validate the model using data on the historical range of HLB.Our model predicts that transmission of HLB is possible between 16°C and 33°C with peak transmission at ~25°C. The greatest uncertainty in our suitability metric is associated with the mortality of the vectors at peak transmission, and fecundity at the edges of the thermal range, indicating that these parameters need further experimental work.We produce global thermal niche maps by plotting how many months each location is suitable for establishment of the pest/disease. This analysis reveals that the highest suitability for HLB occurs near the equator in large citrus-producing regions, such as Brazil and South-East Asia. Within the northern hemisphere, the Iberian peninsula and California are HLB suitable for up to 7 months of the year and are free of HLB currently.Policy implications. The thermal niche map indicates the places at greatest risk of HLB establishment should the disease enter these regions. This indicates where surveillance should be focused to prevent establishment. Our mechanistic method can be used to predict new areas for HLB transmission under different climate change scenarios and is easily adapted to other vector-borne diseases.
Memory in trait macroevolution
Authors: Goldberg Emma E. , Foo Jasmine 
Published: November 2018

AbstractThe history of a trait within a lineage may influence its future evolutionary trajectory, but macroevolutionary theory of this process is not well developed. For example, consider the simple binary trait of living in cave versus surface habitat. The longer a species has been cave-dwelling, the more may accumulated loss of vision, pigmentation, and defense restrict future adaptation if the species encounters the surface environment. However, the Markov model of discrete trait evolution that is widely adopted in phylogenetics does not allow the rate of cave-to-surface transition to decrease with longer duration as a cave-dweller. Here, we describe three models of evolution that remove this ‘memory-less’ constraint, using a renewal process to generalize beyond the typical Poisson process of discrete trait macroevolution. We then show how the two-state renewal process can be used for inference, and we investigate the potential of phylogenetic comparative data to reveal different influences of trait duration, or ‘memory’ in trait evolution. We hope that such approaches may open new avenues for modeling trait evolution and for broad comparative tests of hypotheses that some traits become entrenched.
Inference of Differential Gene Regulatory Networks Based on Gene Expression and Genetic Perturbation Data
Authors: Zhou Xin , Cai Xiaodong 
Published: November 2018

AbstractMotivationGene regulatory networks (GRNs) of the same organism can be different under different conditions, although the overall network structure may be similar. Understanding the difference in GRNs under different conditions is important to understand condition-specific gene regulation. When gene expression and other relevant data under two different conditions are available, they can be used by an existing network inference algorithm to estimate two GRNs separately, and then to identify the difference between the two GRNs. However, such an approach does not exploit the similarity in two GRNs, and may sacrifice inference accuracy.ResultsIn this paper, we model GRNs with the structural equation model (SEM) that can integrate gene expression and genetic perturbation data, and develop an algorithm named fused sparse SEM (FSSEM), to jointly infer GRNs under two conditions, and then to identify difference of the two GRNs. Computer simulations demonstrate that the FSSEM algorithm outperforms the approach that estimates two GRNs separately. Analysis of a gene expression and SNP dataset of lung cancer and normal lung tissues with FSSEM inferred a GRN largely agree with the known lung GRN reported in the literature, and it identified a differential GRN, whose genes with largest degrees were reported to be implicated in lung cancer. The FSSEM algorithm provides a valuable tool for joint inference of two GRNs and identification of the differential GRN under two conditions.AvailabilityThe software package for the FSSEM algorithm is available at https://github.com/Ivis4ml/FSSEM.gitContactx.cai@miami.edu
An Analysis of Characterized Plant Sesquiterpene Synthases
Authors: Durairaj Janani , Girolamo Alice Di , Bouwmeester Harro J , de Ridder Dick , Beekwilder Jules , van Dijk Aalt DJ 
Published: November 2018

AbstractPlants exhibit a vast array of sesquiterpenes, C15 hydrocarbons which often function as herbivore-repellents or pollinator-attractants. These in turn are produced by a diverse range of sesquiterpene synthases. A comprehensive analysis of these enzymes in terms of product specificity has been hampered by the lack of a centralized resource of sufficient functionally annotated sequence data. To address this, we have gathered 262 plant sesquiterpene synthase sequences with experimentally characterized products. The annotated enzyme sequences allowed for an analysis of terpene synthase motifs, leading to the extension of one motif and recognition of a variant of another. In addition, putative terpene synthase sequences were obtained from various resources and compared with the annotated sesquiterpene synthases. This analysis indicated regions of terpene synthase sequence space which so far are unexplored experimentally. Finally, we present a case describing mutational studies on residues altering product specificity, for which we analyzed conservation in our database. This demonstrates an application of our database in choosing likely-functional residues for mutagenesis studies aimed at understanding or changing sesquiterpene synthase product specificity.
A Modified Hodgkin-Huxley model to Show the Effect of Motor Cortex Stimulation on the Trigeminal Neuralgia Network
Authors: Khodashenas Mohammadreza , Baghdadi Golnaz , Towhidkhah Farzad 
Published: November 2018

AbstractBackgroundTrigeminal neuralgia (TN) is a severe neuropathic pain, which has an electric shock like characteristic. There are some common treatments for this pain such as medicine, microvascular decompression or radio frequency. In this regard, transcranial direct current stimulation (tDCS) is another therapeutic method to reduce the pain, which has been recently attracting the therapists’ attention. The positive effect of tDCS on TN was shown in many previous studies. However, the mechanism of tDCS effect has remained unclearObjectiveThis study aims to model the neuronal behavior of the main known regions of the brain participating in TN pathways to study the effect of transcranial direct current stimulationMethodThe proposed model consists of several blocks (block diagram): 1) trigeminal nerve, 2) trigeminal ganglion, 3) PAG (Periaqueductal gray in the brainstem), 4) thalamus, 5) motor cortex (M1) and 6) somatosensory cortex (S1). Each of these components represented by a modified Hodgkin-Huxley (HH) model (a mathematical model). The modification of the HH model was done based on some neurological facts of pain sodium channels. The input of the model is any stimuli to ‘trigeminal nerve,’ which cause the pain, and the output is the activity of the somatosensory cortex. An external current, which is considered as electrical current, was applied to the motor cortex block of the modelResultThe results showed that by decreasing the conductivity of the slow sodium channels (pain channels) and applying tDCS over the M1, the activity of the somatosensory cortex would be reduced. This reduction can cause pain reliefConclusionThe proposed model provided some possible suggestions about the relationship between the effects of tDCS and associated components in TN, and also the relationship between the pain measurement index, somatosensory cortex activity, and the strength of tDCS.
Single-cell RNA sequencing reveals a dynamic stromal niche within the evolving tumour microenvironment
Authors: Davidson Sarah , Efremova Mirjana , Riedel Angela , Mahata Bidesh , Pramanik Jhuma , Huuhtanen Jani , Kar Gozde , Vento-Tormo Roser , Hagai Tzachi , Chen Xi , Haniffa Muzlifah A. , Shields Jacqueline D. , Teichmann Sarah A. 
Published: November 2018

SummaryNon-cancerous stromal cells represent a highly diverse compartment of the tumour, yet their role across tumour evolution remains unclear. We employed single-cell RNA sequencing to determine stromal adaptations in murine melanoma at different points of tumour development. Naive lymphocytes recruited from lymph nodes underwent activation and clonal expansion within the tumour, prior to PD1 and Lag3 expression, while tumour-associated myeloid cells promoted the formation of a suppressive niche through cytokine secretion and inhibitory T cell interactions. We identified three temporally distinct cancer-associated fibroblast (CAF) populations displaying unique signatures, and verified these in human datasets. In early tumours, immune CXCL12/CSF1 and complement-expressing CAFs supported recruitment of macrophages, whereas contractile CAFs became more prevalent in later tumours. This study highlights the complex interplay and increasing diversity among cells that co-evolve with the tumour, indicating that from early stages of development, stromal cells acquire the capacity to modulate the immune landscape towards suppression.
Behavioral evolution drives hindbrain diversification among Lake Malawi cichlid fish
Authors: York Ryan A. , Byrne Allie , Abdhilleh Kawther , Patil Chinar , Streelman J. Todd , Finger Thomas E. , Fernald Russell D. 
Published: November 2018

AbstractThe evolutionary diversification of animal behavior is often associated with changes in the structure and function of nervous systems. Such evolutionary changes arise either through alterations of individual neural components (“mosaically”) or through scaling of the whole brain (“conceitedly”). Here we show that the evolution of a specific courtship behavior in Malawi cichlid fish, the construction of mating nests known as bowers, is associated with rapid, extensive, and specific diversification of orosensory, gustatory centers in the hindbrain. We find that hindbrain volume varies significantly between species that build pit (depression) compared to castle (mound) type bowers and that hindbrain features evolve rapidly and independently of phylogeny among castle-building species. Using immediate early gene expression, we confirmed a functional role for hindbrain structures during bower building. Comparisons of bower building species in neighboring Lake Tanganyika show patterns of neural diversification parallel to those in Lake Malawi. Our results suggest that mosaic brain evolution via alterations to individual brain structures is more extensive and predictable than previously appreciated.
Variability in the Analgesic Response to Ibuprofen Following Third-Molar Extraction is Associated with Differences in Activation of the Cyclooxygenase Pathway
Authors: Theken Katherine N. , Hersh Elliot V. , Lahens Nicholas F. , Lee Hyo Min , Granquist Eric J. , Giannakopoulos Helen , Levin Lawrence M. , Secreto-Dankanich Stacey A. , Grant Gregory R. , Detre John A. , FitzGerald Garret A. , Grosser Tilo , Farrar John T. 
Published: November 2018

AbstractThe analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized to be limited by substantial interindividual variability in pain relief, but the underlying mechanisms are not well understood. We performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars, in order to characterize factors associated with heterogeneity in response to ibuprofen.Subjects were treated with rapid-acting ibuprofen (400 mg; N=19) or placebo (N=10) in a randomized, double-blind design. Compared to placebo, ibuprofen-treated subjects exhibited greater reduction in pain scores, alterations in regional cerebral blood flow in brain regions associated with pain processing, and inhibition of ex vivo cyclooxygenase activity and urinary prostaglandin metabolite excretion as indices of biochemical drug action (p<0.05). As expected, ibuprofen-treated subjects could be stratified into partial responders (N=9, required rescue medication within the dosing interval) and complete responders (N=10, no rescue medication). This was also reflected by differences in pain scores (p<0.01) as early as 30 minutes following drug administration (p<0.05). Variability in analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, metabolizing enzyme genotype, or the degree of cyclooxygenase inhibition by ibuprofen. However, complete responders had higher concentrations of inflammatory biomarkers in urine and serum, than partial responders. Specifically, a stable urinary prostaglandin E2metabolite, serum TNFα and IL-8 were higher in patients who did not require rescue medication compared those who did (p < 0.05). RNAseq gene expression analysis in PBMCs collected after surgery and ibuprofen administration showed enrichment of inflammation related pathways among genes differentially expressed (q < 0.2) between complete and partial respondersThese findings suggest that patients who receive substantial pain relief from ibuprofen have a more pronounced activation of the prostanoid biosynthetic pathway and regulation of the inflammatory pain phenotype differs from those patients who are insufficiently treated with ibuprofen alone and may require an opioid or other therapeutic intervention.
Germline deletion reveals a non-essential role of the atypical MAPK6/ERK3
Authors: Ronkina N. , Schuster-Gossler K. , Hansmann F. , Kunze-Schumacher H. , Sandrock I. , Yakovleva T. , Lafera J. , Baumgärtner W. , Krueger A. , Prinz I. , Gossler A. , Kotlyarov A. , Gaestel M. 
Published: November 2018

AbstractMAPK6/ERK3 is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary disfunction and by defects in function, activation and positive selection of T cells. To study the role of ERK3in vivo, we generated mice carrying a conditionalErk3allele with exon3 flanked by LoxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-creand a clear reduction of the protein kinase MK5 is detected, providing first evidence for the existence of the ERK3/MK5 signaling complexin vivo.In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile, do not display pulmonary hypoplasia, acute respiratory failure, abnormal T cell development, reduction of thymocyte numbers or altered T cells selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality, lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin-resistance-cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal suggesting redundant functions of both protein kinases.
Embracing the dropouts in single-cell RNA-seq data
Authors: Qiu Peng 
Published: November 2018

AbstractOne primary reason that makes the analysis of single-cell RNA-seq data challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Many computational algorithms developed for single-cell RNA-seq adopted gene selection and dimension reduction strategies to address the dropouts. Here, an opposite view is explored. Instead of treating dropouts as a problem to be fixed, we embrace it as a useful signal for defining cell types. We present an iterative co-occurrence clustering algorithm that works with binarized single-cell RNA-seq count data. Surprisingly, although all the quantitative information is removed after the data is binarized, co-occurrence clustering of the binarized data is able to effectively identify cell populations, as well as cell-type specific pathways. We demonstrate that the binary dropout patterns of the data provides not only overlapping but also complementary information compared to the quantitative gene expression counts in single-cell RNA-seq data.
Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling
Authors: Liang Qingnan , Dharmat Rachayata , Owen Leah , Shakoor Akbar , Li Yumei , Kim Sangbae , Vitale Albert , Kim Ivana , Morgan Denise , Wu Nathaniel , DeAngelis Margaret , Chen Rui 
Published: November 2018

ABSTRACTGene expression profiling is an effective way to provide insights into cell function. However, for heterogeneous tissues, bulk RNA-Seq can only provide the average gene expression profile for all cells from the tissue, making the interpretation of the sequencing result challenging. Single-cell RNA-seq, on the other hand, generates transcriptomic profiles of individual cell and cell types, making it a powerful method to decode the heterogeneity in complex tissues.The retina is a heterogeneous tissue composed of multiple cell types with distinct functions. Here we report the first single-nuclei RNA-seq transcriptomic study on human neural retinal tissue to identify transcriptome profile for individual cell types. Six retina samples from three healthy donors were profiled and RNA-seq data with high quality was obtained for 4730 single nuclei. All seven major cell types were observed from the dataset and signature genes for each cell type were identified by differential gene express analysis. The gene expression of the macular and peripheral retina was compared at the cell type level, showing significant improvement from previous bulk RNA-seq studies. Furthermore, our dataset showed improved power in prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrated that feasibility of obtaining single cell transcriptome from human frozen tissues to provide additional insights that is missed by either the human bulk RNA-seq or the animal models.
Polymerization Kinetics Stability, Volumetric Changes, Apatite Precipitation, Strontium Release and Fatigue of Novel Bone Composites for Vertebroplasty
Authors: Panpisut Piyaphong , Main Kirsty , Adnan Khan Muhammad , Arshad Mayda , Xia Wendy , Petridis Haralampos , Margaret Young Anne 
Published: November 2018

AbstractPurposeThe aim was to determine effects of diluent monomer and monocalcium phosphate monohydrate (MCPM) on polymerization kinetics and volumetric stability, apatite precipitation, strontium release and fatigue of novel dual-paste composites for vertebroplasty.Materials and methodsPolypropylene (PPGDMA) or triethylene (TEGDMA) glycol dimethacrylates (25 wt%) diluents were combined with urethane dimethacrylate (70 wt%) and hydroxyethyl methacrylate (5 wt%). 70 wt% filler containing glass particles, glass fibers (20 wt%) and polylysine (5 wt%) was added. Benzoyl peroxide and MCPM (10 or 20 wt%) or N-tolyglycine glycidyl methacrylate and tristrontium phosphate (15 wt%) were included to give initiator or activator pastes. Commercial PMMA (Simplex) and bone composite (Cortoss) were used for comparison.ATR-FTIR was used to determine thermal activated polymerization kinetics of initiator pastes at 50-80 °C. Paste stability, following storage at 4-37 °C, was assessed visually or through mixed paste polymerization kinetics at 25 °C. Polymerization shrinkage and heat generation were calculated from final monomer conversions. Subsequent expansion and surface apatite precipitation in simulated body fluid (SBF) were assessed gravimetrically and via SEM. Strontium release into water was assessed using ICP-MS. Biaxial flexural strength (BFS) and fatigue properties were determined at 37 °C after 4 weeks in SBF.ResultsPolymerization profiles all exhibited an inhibition time before polymerization as predicted by free radical polymerization mechanisms. Initiator paste inhibition times and maximum reaction rates were described well by Arrhenius plots. Plot extrapolation, however, underestimated lower temperature paste stability. Replacement of TEGDMA by PPGDMA, enhanced paste stability, final monomer conversion, water-sorption induced expansion and strontium release but reduced polymerisation shrinkage and heat generation. Increasing MCPM level enhanced volume expansion, surface apatite precipitation and strontium release. Although the experimental composite flexural strengths were lower compared to those of commercially available Simplex, the extrapolated low load fatigue lives of all materials were comparable.ConclusionsIncreased inhibition times at high temperature give longer predicted shelf-life whilst stability of mixed paste inhibition times is important for consistent clinical application. Increased volumetric stability, strontium release and apatite formation should encourage bone integration. Replacing TEGDMA by PPGDMA and increasing MCPM could therefore increase suitability of the above novel bone
composites for vertebroplasty. Long fatigue lives of the composites may also ensure long-term durability of the materials.