bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Indocyanine Green on Hepatic Gd-EOB-DTPA Uptake
Authors: Akai Hiroyuki , Yasaka Koichiro , Nojima Masanori , Inoue Yusuke , Ohtomo Kuni , Kiryu Shigeru 
Published: February 2017

Objectives
The aim of this study was to explore the influence of indocyanine green (ICG) on hepatic uptake of gadolinium ethoxybenzyldiethylenetriaminepenta-acetic acid (Gd-EOB-DTPA).

Materials and Methods
Groups of 6 female C57BL6 mice were injected with 5 mg/kg ICG, 20 mg/kg ICG, or phosphate-buffered saline (control group) 10 minutes before the injection of Gd-EOB-DTPA; identical 3-dimensional gradient echo T1-weighted images were subsequently obtained to create time-intensity curves and to measure the peak contrast ratios (CRs) of liver parenchyma. We studied both hypothermic and normothermic mice. Peak CRs for all experimental conditions were evaluated, and among-group differences were assessed using 2-way factorial analysis of variance with Bonferroni post hoc testing.

Results
In hypothermic mice, the time-intensity curves of the 3 groups gradually increased from 5 to 30 minutes and almost plateaued after 30 minutes. The peak CR decreased as the amount of injected ICG increased (control group, 5 mg/kg ICG, 20 mg/kg ICG: 1.66 ± 0.09, 1.37 ± 0.18, 1.25 ± 0.24, respectively). In normothermic animals, the time-intensity curves of the control and ICG 5 mg/kg groups peaked 10 to 15 minutes after injection, the peak CRs were very similar (control group, 5 mg/kg ICG: 2.01 ± 0.16, 1.95 ± 0.14, respectively), and the intensities thereof then gradually fell until 60 minutes. Compared with these groups, the ICG 20 mg/kg group exhibited lower peak CR (1.48 ± 0.14) and a weaker decrease in intensity to 60 minutes. Both the amount of ICG injected (P < 0.001) and the experimental temperature (P < 0.001) significantly affected the measurements.

Conclusions
Indocyanine green inhibits the hepatic uptake of Gd-EOB-DTPA and affects the signal intensity upon Gd-EOB-DTPA–enhanced magnetic resonance imaging. Such inhibition was more obvious in hypothermic mice.
Single-cell transcriptomics of malaria parasites
Authors: Reid Adam J. , Talman Arthur M. , Bennett Hayley M. , Gomes Ana R. , Sanders Mandy J. , Illingworth Christopher J. R. , Billker Oliver , Berriman Matthew , Lawniczak Mara K. N. 
Published: February 2017

AbstractSingle-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations, but has not yet been applied to single cell organisms. Here, we established a method to successfully investigate transcriptional variation across individual malaria parasites. We discover an unexpected, discontinuous program of transcription during asexual growth previously masked by bulk analyses, and uncover novel variation among sexual stage parasites in their expression of gene families important in host-parasite interactions.
High-Throughput Controlled Mechanical Stimulation and Functional ImagingIn Vivo
Authors: Cho Yongmin , Porto Daniel A. , Hwang Hyundoo , Grundy Laura J. , Schafer William R. , Lu Hang 
Published: February 2017

AbstractUnderstanding mechanosensation and other sensory behavior in genetic model systems such asC. elegansis relevant to many human diseases. These studies conventionally require immobilization by glue and manual delivery of stimuli, leading to low experimental throughput and high variability. Here we present a microfluidic platform that delivers precise mechanical stimuli robustly. The system can be easily used in conjunction with functional imaging and optical interrogation techniques, as well as other capabilities such as sorting or more sophisticated fluid delivery schemes. The platform is fully automated, thereby greatly enhancing the throughput and robustness of experiments. We show that behavior of the well-known gentle and harsh touch neurons and their receptive fields can be recapitulated in our system. Using calcium dynamics as a readout, we demonstrate the ability to perform a drug screenin vivo. Furthermore, using an integrated chip platform that can deliver both mechanical and chemical stimuli, we examine sensory integration in interneurons in response to multimodal sensory inputs. We envision that this system will be able to greatly accelerate the discovery of genes and molecules involved in mechanosensation and multimodal sensory behavior, as well as the discovery of therapeutics for related diseases.
Single-Neuron Gene Expression Analysis Using the Maxwell® 16 LEV System in the Neural Systems and Behavior Course
Authors: Harris Rayna M. , Otopalik Adriane G. , Smith Colin J. , Bucher Dirk , Golowasch Jorge , Hofmann Hans A. 
Published: February 2017

ABSTRACTGene expression analysis from single cells has become increasingly prominent across biological disciplines; thus, it is important to train students in these approaches. Here, we present an experimental and analysis pipeline that we developed for the Neural Systems & Behavior (NS&B) course at Marine Biological Laboratory. Our approach used the Maxwell®16 LEV simplyRNA Tissue Kit and GoTaq®2-Step RT-qPCR System for gene expression analysis from single neurons of the crustacean stomatogastric ganglion, a model system to study the generation of rhythmic motor patterns. We used double-stranded RNA to knockdown expression of a putative neuromodulator-activated sodium channel. We then examined the electrophysiological responses to known neuromodulators and confirmed that the response was reduced. Finally, we measured how mRNA levels of several ion channel genes changed in response. Our results provide new insights into the neural mechanisms underlying the generation and modulation of rhythmic motor patterns.
Epidemic network analysis for mitigation of invasive pathogens in seed systems: Potato in Ecuador
Authors: Buddenhagen C. E. , Hernandez Nopsa J. F. , Andersen K. F. , Andrade-Piedra J. , Forbes G. A. , Kromann P. , Thomas-Sharma S. , Useche P. , Garrett K. A. 
Published: February 2017

AbstractSeed systems have an important role in the distribution of high quality seed and improved varieties. The structure of seed networks also helps to determine the epidemiological risk for seedborne disease. We present a new method for evaluating the epidemiological role of nodes in seed networks, and apply it to a regional potato farmer consortium (CONPAPA) in Ecuador. We surveyed farmers to estimate the structure of networks of farmer seed tuber and ware potato transactions, and farmer information sources about pest and disease management. Then we simulated pathogen spread through seed transaction networks to identify priority nodes for disease detection. The likelihood of pathogen establishment was weighted based on the quality and/or quantity of information sources about disease management. CONPAPA staff and facilities, a market, and certain farms are priorities for disease management interventions, such as training, monitoring and variety dissemination. Advice from agrochemical store staff was common but assessed as significantly less reliable. Farmer access to information (reported number and quality of sources) was similar for both genders. Women had a smaller amount of the market share for seed-tubers and ware potato, however. Understanding seed system networks provides input for scenario analyses to evaluate potential system improvements.
Quiescent Body as a Reversible Subcellular Structure Formed in Non-growing Bacterial Cells
Authors: Yu Jiayu , Liu Yang , Yin Huijia , Chang Zengyi 
Published: February 2017

SummaryBacterial cells take a variable lag time and maintain a multi-drug tolerant non-growing state before resuming growth when encountering growth-supportive conditions. Some of them exhibit an extraordinarily long lag, as pathogenic persisters do. It remains unknown on what determines lag time duration. Here, we unveiled a subcellular structure, termed quiescent body, that is formed in bacterial cells entering non-growing state and sequesters selected proteins essential for cell growth. Their formation occurs progressively in each cell and heterogeneously among individual cells. They only dissolve in re-growing cells to release proteins for immediate re-functioning when conditions become fit. Quiescent body, whose degree of formation is highly correlated with duration of lag time or level of antibiotic tolerance, apparently functions as a biological timer for bacterial growth resumption. Further, suppressing their formation, which directly relies on cellular respiration complexes, or promoting their dissolution might be a viable strategy to eradicate persisters.
Stratified Linkage Disequilibrium Score Regression reveals enrichment of eQTL effects on complex traits is not tissue specific
Authors: Ip Hill F. , Jansen Rick , Abdellaoui Abdel , Bartels Meike ,   UK Brain Expression Consortium, Boomsma Dorret I. , Nivard Michel G. 
Published: February 2017

AbstractBoth gene expression levels and eQTLs (expression quantitative trait loci) are partially tissue-specific, complicating the detection of eQTLs in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be non-trivial, allowing for inference of eQTL functioning in the brain via eQTLs measured in readily accessible tissues, e.g. whole blood. Using Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantify the enrichment in GWAS signal of blood and brain eQTLs in genome-wide association study (GWAS) on 11 complex traits (schizophrenia, BMI, educational attainment, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, age at menarche, coronary artery disease, height, LDL levels, and smoking behavior). Our analyses established significant enrichment of blood and brain eQTLs in their effects across all traits. As we do not know the true number of causal eQTLs, it is difficult to determine the precise magnitude of enrichment. We found no evidence for tissue-specific enrichment in GWAS signal for either eQTLs uniquely seen in the brain or whole blood. To follow up on our findings, we tested tissue-specific enrichment of eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium, and, again, found no tissue-specific eQTL effects. We further integrated the GTEx eQTLs with SNPs associated with tissue-specific histone modifiers, and interrogate its effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects on schizophrenia, though again not tissue-specific. Finally, we extracted eQTLs in tissue-specific differentially expressed genes, and determined their effects on rheumatoid arthritis and schizophrenia. We conclude that, while eQTLs are strongly enriched in GWAS signal, the enrichment is not specific to the tissue used in eQTL discovery. Therefore, working with relatively accessible tissues, such as whole blood, as proxy for eQTL discovery is sensible; and restricting lookups for GWAS hits to a specific tissue might not be advisable.
Genomic contingencies and beak shape variation in a hybrid species
Authors: Runemark Anna , Fernández Laura Piñeiro , Eroukhmanoff Fabrice , Sætre GlennPeter 
Published: February 2017

AbstractHybridization is increasingly recognized as a potent evolutionary force. Though additive genetic variation and novel combinations of parental genes theoretically increase the potential for hybrid species to adapt, few empirical studies have investigated the adaptive potential within a hybrid species. Here, we investigate factors promoting phenotypic divergence using genomically diverged island populations of the homoploid hybrid Italian sparrowPasser italiaefrom Crete, Corsica, and Sicily. We address whether genomic contingencies, adaptation to climate or diet best explain divergence in beak morphology. Populations vary significantly in beak morphology, both between and within islands of origin. Temperature seasonality best explains population divergence in beak size. Interestingly, beak shape along all significant dimensions of variation was best explained by annual precipitation, genomic composition and their interaction, suggesting a role for contingencies. Moreover, beak shape similarity to a parent species correlates with proportion of the genome inherited from that species, consistent with the presence of contingencies. In conclusion, adaptation to local conditions and genomic contingencies arising from putatively independent hybridization events jointly explain beak morphology in the Italian sparrow. Hence, hybridization may induce contingencies and restrict evolution in certain directions dependent on the genetic background.
Variation and constraints in hybrid genome formation
Authors: Runemark Anna , Trier Cassandra N. , Eroukhmanoff Fabrice , Hermansen Jo S. , Matschiner Michael , Ravinet Mark , Elgvin Tore O. , Sætre Glenn-Peter 
Published: February 2017

SummaryRecent genomic investigations have revealed hybridization to be an important source of variation, the working material of natural selection1,2. Hybridization can spur adaptive radiations3, transfer adaptive variation across species boundaries4, and generate species with novel niches5. Yet, the limits to viable hybrid genome formation are poorly understood. Here we investigated to what extent hybrid genomes are free to evolve or whether they are restricted to a specific combination of parental alleles by sequencing the genomes of four isolated island populations of the homoploid hybrid Italian sparrowPasser italiae6,7. Based on 61 Italian sparrow genomes from Crete, Corsica, Sicily and Malta, and 10 genomes of each of the parent speciesP. domesticusandP. hispaniolensis,we report that a variety of novel and fully functional hybrid genomic combinations have arisen on the different islands, with differentiation in candidate genes for beak shape and plumage colour. There are limits to successful genome fusion, however, as certain genomic regions are invariably inherited from the same parent species. These regions are overrepresented on the Z-chromosome and harbour candidate incompatibility loci, including DNA-repair and mito-nuclear genes; loci that may drive the general reduction of introgression on sex chromosomes8. Our findings demonstrate that hybridization is a potent process for generating novel variation, but variation is limited by DNA-repair and mito-nuclear genes, which play an important role in reproductive isolation and thus contribute to speciation.
Stochastic satisficing account of confidence in uncertain value-based decisions
Authors: Hertz Uri , Bahrami Bahador , Keramati Mehdi 
Published: February 2017

AbstractEvery day we make choices under uncertainty; choosing what route to work or which queue in a supermarket to take, for example. It is unclear how outcome variance, e.g. uncertainty about waiting time in a queue, affects decisions and confidence when outcome is stochastic and continuous. How does one evaluate and choose between an option with unreliable but high expected reward, and an option with more certain but lower expected reward? Here we used an experimental design where two choices’ payoffs took continuous values, to examine the effect of outcome variance on decision and confidence. We found that our participants’ probability of choosing the good (high expected reward) option decreased when the good or the bad options’ payoffs were more variable. Their confidence ratings were affected by outcome variability, but only when choosing the good option. Unlike perceptual detection tasks, confidence ratings correlated only weakly with decisions’ time, but correlated with the consistency of trial-by-trial choices. Inspired by the satisficing heuristic, we propose a “stochastic satisficing” (SSAT) model for evaluating options with continuous uncertain outcomes. In this model, options are evaluated by their probability of exceeding an acceptability threshold, and confidence reports scale with the chosen option’s thus-defined satisficing probability. Participants’ decisions were best explained by an expected reward model, while the SSAT model provided the best prediction of decision confidence. We further tested and verified the predictions of this model in a second experiment. Our model and experimental results generalize the models of metacognition from perceptual detection tasks to continuous-value based decisions. Finally, we discuss how the stochastic satisficing account of decision confidence serves psychological and social purposes associated with the evaluation, communication and justification of decision-making.Author SummaryEvery day we make several choices under uncertainty, like choosing a queue in a supermarket. However, the computational mechanisms underlying such decisions remain unknown. For example, how does one choose between an option with unreliable high expected reward, like the volatile express queue, and an option with more certain but lower expected reward in the standard queue? Inspired by bounded rationality and the notion of ‘satisficing’, i.e. settling for a good enough option, we propose that such decisions are made by comparing the likelihood of different actions to surpass an acceptability threshold. When facing uncertain decisions, our participants’ confidence ratings were not consistent with the expected outcome’s rewards, but instead followed the satisficing heuristic proposed here. Using an acceptability threshold may be especially useful when evaluating and justifying decisions under uncertainty.
Wild tobacco genomes reveal the evolution of nicotine biosynthesis
Authors: Xu Shuqing , Brockmöller Thomas , Navarro-Quezada Aura , Kuhl Heiner , Gase Klaus , Ling Zhihao , Zhou Wenwu , Kreitzer Christoph , Stanke Mario , Tang Haibao , Lyons Eric , Pandey Priyanka , Pandey Shree P. , Timmermann Bernd , Gaquerel Emmanuel , Baldwin Ian T. 
Published: February 2017

AbstractNicotine, the signature alkaloid ofNicotianaspecies responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos,Nicotiana attenuata(2.5 Gb) andN. obtusifolia(1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated theseNicotianagenomes, promoted expression divergences among duplicated genes and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinic acid dinucleotide (NAD) pathways. While the duplication of the former is shared among several Solanaceous genera which produce polyamine-derived tropane alkaloids, the innovation and efficient production of nicotine in the genusNicotianarequired lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor (ERF) that activates the expression of all nicotine biosynthetic genes. Furthermore, TE insertions that incorporated transcription factor binding motifs also likely contributed to the coordinated metabolic flux of the nicotine biosynthetic pathway. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.
Multi-tissue polygenic models for transcriptome-wide association studies
Authors: Park Yongjin , Sarkar Abhishek , Bhutani Kunal , Kellis Manolis 
Published: February 2017

I.ABSTRACTTranscriptome-wide association studies (TWAS) have proven to be a powerful tool to identify genes associated with human diseases by aggregating cis-regulatory effects on gene expression. However, TWAS relies on building predictive models of gene expression, which are sensitive to the sample size and tissue on which they are trained. The Gene Tissue Expression Project has produced reference transcriptomes across 53 human tissues and cell types; however, the data is highly sparse, making it difficult to build polygenic models in relevant tissues for TWAS. Here, we propose fQTL, a multi-tissue, multivariate model for mapping expression quantitative trait loci and predicting gene expression. Our model decomposes eQTL effects into SNP-specific and tissue-specific components, pooling information across relevant tissues to effectively boost sample sizes. In simulation, we demonstrate that our multi-tissue approach outperforms single-tissue approaches in identifying causal eQTLs and tissues of action. Using our method, we fit polygenic models for 13,461 genes, characterized the tissue-specificity of the learnedcis-eQTLs, and performed TWAS for Alzheimer’s disease and schizophrenia, identifying 107 and 382 associated genes, respectively.
Targeted sequencing of venom genes from cone snail genomes reveals coupling between dietary breadth and conotoxin diversity
Authors: Phuong Mark A , Mahardika Gusti N 
Published: February 2017

AbstractAlthough venomous taxa provide an attractive system to study the genetic basis of adaptation and speciation, the slow pace of toxin gene discovery through traditional laboratory techniques (e.g., cDNA cloning) have limited their utility in the study of ecology and evolution. Here, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and non-toxin loci from the genomes of 32 species of cone snails (family, Conidae), a hyper diverse group of carnivorous marine gastropods that capture their prey using a cocktail of neurotoxic proteins (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species sequenced in this study with high confidence (> 100X coverage). We found that conotoxin gene superfamilies are composed of 1-6 exons and adjacent noncoding regions are not enriched for simple repetitive elements. Additionally, we provided further evidence for several genetic factors shaping venom composition in cone snails, including positive selection, extensive gene turnover, expression regulation, and potentially, presence-absence variation. Using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin gene superfamily size evolution, dietary breadth was positively correlated with total conotoxin gene diversity. These results continue to emphasize the importance of dietary breadth in shaping venom evolution, an underappreciated ecological correlate in venom biology. Finally, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification.
SUPERMANprevents stamen formation and promotes stem cell termination in the fourth whorl of the Arabidopsis flower
Authors: Prunet Nathanaël , Yang Weibing , Das Pradeep , Meyerowitz Elliot M. , Jack Thomas P. 
Published: February 2017

SummaryThe molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. TheSUPERMANgene is required for proper specification of the boundary between stamens in whorl 3 and carpels in whorl 4, assupermanmutants exhibit supernumerary stamens but usually lack carpels. However, it has remained unclear whether extra stamens insupermanmutants originate from an organ identity change in whorl 4 or the overproliferation of whorl 3. Using live confocal imaging, we show that the extra stamens insupermanmutants arise from cells in whorl 4, which change their fate from female to male, while floral stem cells proliferate longer, allowing for the production of additional stamens.