bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the discovery of subpopulation-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data
Authors: Crowell Helena L. , Soneson Charlotte , Germain Pierre-Luc , Calini Daniela , Collin Ludovic , Raposo Catarina , Malhotra Dheeraj , Robinson Mark D. 
Published: July 2019

AbstractSingle-cell RNA sequencing (scRNA-seq) has quickly become an empowering technology to profile the transcriptomes of individual cells on a large scale. Many early analyses of differential expression have aimed at identifying differences between subpopulations, and thus are focused on finding subpopulation markers either in a single sample or across multiple samples. More generally, such methods can compare expression levels in multiple sets of cells, thus leading to cross-condition analyses. However, given the emergence of replicated multi-condition scRNA-seq datasets, an area of increasing focus is making sample-level inferences, termed here as differential state analysis. For example, one could investigate the condition-specific responses of cell subpopulations measured from patients from each condition; however, it is not clear which statistical framework best handles this situation. In this work, we surveyed the methods available to perform cross-condition differential state analyses, including cell-level mixed models and methods based on aggregated “pseudobulk” data. We developed a flexible simulation platform that mimics both single and multi-sample scRNA-seq data and provide robust tools for multi-condition analysis within the muscat R package.
Fluorometric intracellular Na+ measurement as compared with flame emission assay: An unexpected problem with gramicidin-based calibration
Authors: Yurinskaya Valentina E. , Aksenov Nikolay D. , Moshkov Alexey V. , Goryachaya Tatyana S. , Vereninov Alexey A. 
Published: July 2019

AbstractFluorescent probes are a popular and indispensable tool for monitoring sodium concentration in living cells in situ. Calibration of fluorescent probes inside cells commonly uses ionophores to equilibrate intracellular and external ion concentrations. Here we test this calibration method using in parallel classical flame emission assay. Suspension human lymphoma cells allow both flow cytometry fluorometric study and flame emission assay. The most sensitive Na+ fluorescent probe ANG-2 and the most common ionophores were tested. Cellular Na+ was altered for calibration in three different ways: by stopping the sodium pump with ouabain, by inducing of apoptosis with staurosporine, and by gramicidin or amphotericin B treatment. We found that ANG-2 fluorescence in cells treated with gramicidin or amphotericin was about two fold lower than in the cells with the same sodium concentration but without ionophores. The equal fluorescence measured in the absence and in the presence of ionophores corresponds to different cell sodium concentrations. No effect of gramicidin on hydrolyzed ANG was observed in vitro. The mechanism, by which gramicidin decreases ANG fluorescence in cells is unlikely to be physical quenching and remains obscure. We conclude that ANG fluorescence does not display realistic cell Na+ if fluorescence in cell is measured in ionophore absence while calibrated in its presence.
Dietary vs non-dietary fatty acid profiles of lake trout ecotypes from Lake Superior and Great Bear Lake: Are fish really what they eat?
Authors: Chavarie L , Hoffmann J. , Muir A.M. , Krueger C.C. , Bronte C.R. , Howland K.L. , Gallagher C.P. , Sitar S.P. , Hansen M.J. , Vinson M.R. , Baker L.F. , Loseto L.L. , Tonn W. , Swanson H. 
Published: July 2019

AbstractFatty acids are well-established biomarkers used to characterize trophic ecology, food-web linkages, and the ecological niche of many different taxa. Most often, fatty acids that are examined include only those previously identified as “dietary” or “extended dietary” biomarkers. Fatty acids considered as non-dietary biomarkers, however, represent numerous fatty acids that can be extracted. Some studies may include non-dietary fatty acids (i.e., combined with dietary fatty acids), but do not specifically assess them, whereas in other studies, these data are discarded. In this study, we explored whether non-dietary biomarkers fatty acids can provide worthwhile information by assessing their ability to discriminate intraspecific diversity within and between lakes. Non-dietary fatty acids used as biomarkers delineated variation among regions, among locations within a lake, and among ecotypes within a species. Physiological differences that arise from differences in energy processing can be adaptive and linked to habitat use by a species’ ecotypes, and likely explains why non-dietary fatty acids biomarkers can be a relevant tool to delineate intraspecific diversity. Little is known about the non-dietary-mediated differences in fatty acid composition, but our results showed that non-dietary fatty acids biomarkers can be useful tool in identifying variation.
The Quantification of Antibody Elements and Receptors subunit expression using qPCR: The Design of VH, VL, CH, CL, FcR subunits primers for a more holistic view of the immune system
Authors: Ling Wei-Li , Ng Yuen-Ling , Wipat Anil , Lane David Philip , Gan Samuel-Ken-En 
Published: July 2019

AbstractThe expression levels of Immunoglobulin elements and their receptors are important markers for health and disease. Within the immunoglobulin locus, the constant regions and the variable region families are associated with certain pathologies, yet a holistic view of the interaction between the expression of the multiple genes remain to be fully characterized. There is thus an important need to quantify antibody elements, their receptors and the receptor subunits in blood (PBMC cDNA) for both screening and detailed studies of such associations. Leveraging on qPCR, we designed primers for all Vκ 1-6, VH1-7, Vλ1-11, nine CH isotypes, Cκ, Cκ, Cλ1 &3, FcεRI α,β, and γ subunits, all three FcγR and their subunits, and FcαR. Validating this on a volunteer PBMC cDNA, we show a qPCR primer set repertoire that can quantify the relative expression of all the above genes to GAPDH housekeeping gene, with implications and uses in both clinical monitoring and research.
Different aspects of social relationships contribute to subjective well-being via different functional connectomes
Authors: Itahashi Takashi , Kosibaty Neda , Hashimoto Ryu-ichiro , Aoki Yuta Y. 
Published: July 2019

AbstractThe achievement of improved subjective well-being (SWB) is a worldwide issue. Prior studies using self-report questionnaires have demonstrated that better social relationships (SR) form the foundation for better SWB. To confirm the relationships with objective measure and investigate the biological underpinning, we conducted connectome-based prediction modeling with a 10-fold cross-validation, utilizing resting state functional magnetic resonance imaging data (n = 761). Two aspects of SWB (life satisfaction and positive affect) were successfully predicted using SR-related functional connections (FCs). The models also showed good prediction performance in a validation sample (n = 91), suggesting that our models are generalizable. All six aspects of SR considered were related to different sets of FCs with minimal overlap in edge level. The contributions of these FC sets to the two aspects of SWB were substantially different. In the future, effort should be made to improve all aspects of SR to achieve better SWB.
Genomic characterization ofVibrio parahaemolyticusfrom Pacific white shrimp and rearing water in Malaysia reveals novel sequence types and structural variation in genomic regions containing thePhotorhabdusinsect-related (Pir) toxin-like genes
Authors: Yan Chrystine Zou Yi , Austin Christopher M. , Ayub Qasim , Rahman Sadequr , Gan Han Ming 
Published: July 2019

AbstractThe Malaysian and global shrimp aquaculture production has been significantly impacted by acute hepatopancreatic necrosis disease (AHPND) typically caused byVibrio parahaemolyticusharboring the pVA plasmid containing thepirAVpandpirBVpgenes which code forPhotorhabdusinsect-related (Pir) toxin. The limited genomic resource forV. parahaemolyticusstrains from Malaysian aquaculture farms precludes an in-depth understanding of their diversity and evolutionary relationships. In this study, we isolated shrimp-associated and environmental (rearing water)V. parahaemolyticusfrom three aquaculture farms located in Northern and Central Malaysia followed by whole-genome sequencing of 40 randomly selected isolates on the Illumina MiSeq. Phylogenomic analysis and multilocus sequence typing (MLST) reveal distinct lineages ofV. parahaemolyticusthat harbor thepirABVpgenes. The recovery of pVA plasmid backbone devoid ofpirAVporpirABVpin someV. parahaemolyticusisolates suggests that the toxin genes are prone to deletion. The new insight gained from phylogenomic analysis of AsianV. parahaemolyticus, in addition to the observed genomic instability of pVa plasmid, will have implications for improvements in aquaculture practices to diagnose, treat or limit the impacts of this disease.
Regulation of neuron-specific gene transcription by stress hormone signalling requires synaptic activity in zebrafish
Authors: Eachus Helen , Subramanya Dheemanth , Jackson Harriet E. , Wang Guannyu , Berntsen Kieran , Ashton John-Paul , Esposito Umberto , Seifuddin Fayaz , Pirooznia Mehdi , Elhaik Eran , Krone Nils , Baines Richard A. , Placzek Marysia , Cunliffe Vincent T. 
Published: July 2019

AbstractThe Glucocorticoid Receptor (GR) co-ordinates metabolic and behavioural responses to stressors. We hypothesised that GR influences behaviour by modulating specific epigenetic and transcriptional processes in the brain. Using the zebrafish as a model organism, the brain methylomes of wild-type and grs357 mutant adults were analysed and GR-sensitive, differentially methylated regions (GR-DMRs) were identified. Two genes with GR-DMRs exhibited distinct methylation and transcriptional sensitivities to GR: the widely expressed direct GR target fkbp5 and neuron-specific aplp1. In larvae, neural activity is required for GR-mediated transcription of aplp1, but not for that of fkbp5. GR regulates metabotropic glutamate receptor gene expression, the activities of which also modulated aplp1 expression, implicating synaptic neurotransmission as an effector of GR function upstream of aplp1. Our results identify two distinct routes of GR-regulated transcription in the brain, including a pathway through which GR couples endocrine signalling to synaptic activity-regulated transcription by modulating metabotropic glutamate receptor expression.
cis dominantly explains regulatory divergence between two indica rice genotypes; drought further enhances regulatory differences
Authors: Ereful Nelzo C. , Laurena Antonio , Liu Li-Yu , Kao Shu-Min , Tsai Eric , Thomson Michael , Greenland Andy , Powell Wayne , Mackay Ian , Leung Hei 
Published: July 2019

AbstractAbstract cis and/or trans regulatory divergence within or between related taxa on a genome-wide scale has been largely unexamined in crops, more so, the effect of stress on cis/trans architecture. In this study, the indica genotypes IR64, an elite drought-susceptible lowland variety, and Apo (IR55423-01 or NSIC RC9), a moderate drought-tolerant upland genotype together with their hybrid (IR64 × Apo) were exposed to non- and water-stress conditions. Evidence of cis and/or trans regulatory differences was tested between these two indica rice genotypes. By sequencing (RNA-seq) the parents and their hybrid, we are able to map genes diverging in cis and/or trans factors between the two genotypes. Under non-stress conditions, cis dominantly explains (11.2%) regulatory differences, followed by trans (8.9%). Further analysis showed that water-limiting conditions largely affect trans and cis + trans factors. Between the two inbred lines, Apo appears to exhibit higher expression fold change of genes enriched in “response to stress” and “photosynthesis” under non- and water-stress conditions. On the molecular level, cis and/or trans regulatory divergence explains their genotypic differences and differential drought response. Parent–hybrid RNA-seq has the potential to identify genes diverging in cis and/or trans factors even between intra-sub-specifically related genotypes. By comparing cis/trans landscape under stressed and unstressed conditions, this approach has the ability to assess the impact of drought on gene expression. Computational analysis and association of several drought-yield QTL markers with cis-diverging genes provide converging evidences suggestive of a potential approach to identify trait-associated candidate genes using hybrids and their parents alone.Key Messagecis dominantly explains divergence of two indica rice genotypes, IR64 and Apo under normal conditions while trans and cis + trans regulatory factors are largely affected by drought
FLASHDeconv: Ultrafast, high-quality feature deconvolution for top-down proteomics
Authors: Jeong Kyowon , Kim Jihyung , Gaikwad Manasi , Hidayah Siti Nurul , Heikaus Laura , Schlüter Hartmut , Kohlbacher Oliver 
Published: July 2019

AbstractFeature deconvolution, the determination of intact proteoform masses, is crucial for top-down proteomics, but currently suffers from long runtimes and quality issues. We present FLASHDeconv, an algorithm based on a simple transformation of mass spectra, which turns deconvolution into the search for constant patterns thus greatly accelerating the process. We show higher deconvolution quality and two to three orders of magnitude faster execution speed than existing approaches.
PyLandStats: An open-source Pythonic library to compute landscape metrics
Authors: Bosch Martí 
Published: July 2019

AbstractQuantifying the spatial pattern of landscapes has become a common task of many studies in landscape ecology. Most of the existing software to compute landscape metrics is not well suited to be used in interactive environments such as Jupyter notebooks nor to be included as part of automated computational workflows. This article presents PyLandStats, an open-source Python library to compute landscape metrics within the scientific Python stack. The PyLandStats package provides a set of methods to undertake recurrent approaches to quantify landscape patterns, such as the analysis of the spatiotemporal patterns of land use/land cover change or gradient analysis. The implementation is based on the prevailing Python libraries for geospatial data analysis in a way that they can be forthwith integrated into complex computational workflows. Notably, the provided methods offer a large variety of options so that users can employ PyLandStats in the way that best supports their needs. The source code is publicly available, and is organized in a modular object-oriented structure that enhances its maintainability and extensibility.
Drug repositoning or target repositioning: a structural perspective of drug-target-indication relationship for available repurposed drugs
Authors: Parisi Daniele , Adasme Melissa F. , Sveshnikova Anastasia , Moreau Yves , Schroeder Michael 
Published: July 2019

ABSTRACTDrug repositioning aims to find new indications for existing drugs, in order to reduce drug development cost and time. Currently, numerous successful stories of drug repositioning have been reported and many drugs are already available on the market. Although many of those cases are products of serendipitous findings, repositioning opportunities can be uncovered systematically by following either a disease-centric approach, as a result of a close relation between an old and new indication, a target-centric one, which links a known target and its established drug to a new indication, or a drug-centric approach, which connects a known drug to a new target and its associated indication. The three approaches differ in their complexity, potential, and limits, and most important the necessary starting information and computational power. Which one is predominant in current drug repositioning and what does this imply for future developments? To address these questions, we systematically evaluated over 100 drugs, 200 targets structures and over 300 indications from the Drug Repositioning Database. Each of the analysed cases has been classified based on one of the three repositioning approaches, showing that the majority, more than 60%, falls within the disease-centric definition, around 30% within the target-centric, and only less than 10% within the drug-centric. We therefore concluded that so far repositioning has mainly been disease and target repositioning and not, as drug repositioning, as expected by definition. We discuss the reasons and suggest directions to exploit the full potential of techniques useful for drug-centric in order to sustain future rationale repositioning pipelines.
TLR4 mediates Il-6 production in irinotecan-induced mucositis
Authors: Khan S. , Bowen J. M. , Wardill Hannah R. 
Published: July 2019

ABSTRACTIntroductionIrinotecan is a first line chemotherapeutic agent for colorectal carcinoma and well known for debilitating diarrhoea caused by mucositis. Tlr4, a pattern recognition receptor, has been implicated in irinotecan -induced mucositis due to its activation of downstream inflammatory pathways and interaction with luminal microbes. Tlr4 deletion has been reported to attenuate mucosal injury in preclinical models of mucositis, hypothesised to occur by blockade of Il-6 production. As such, the current study aimed to determine the relationship between Tlr4 and Il-6 in the context of irinotecan induced mucositis.Materials and methodsArchived ileum and colon tissues from BALB/c wild type (WT) and Tlr4 -/-billy (Tlr4 KO) female mice were used throughout the study. Mice had received single dose of irinotecan (i.p. 270 mg/kg) or vehicle and sacrificed at 6 and 72 hours. Il-6 mRNA and protein expression was determined by qPCR and immunofluorescence, respectively. Data was analysed by Kruskal-Wallis test (qPCR delta CT values) and one-way analysis of variance (ANOVA) (immunofluorescence % area stained).ResultsIl-6 protein expression was significantly reduced in Tlr4 KO mice as compared to WT mice at 6 h in ileum and colon. mRNA expression was not significantly different between groups.ConclusionThese findings support the hypothesis that Tlr4 deletion protects from irinotecan-induced mucositis by ameliorating Il-6 production. The effect appears to be post-transcriptionally mediated, although further research is required to determine if it is via a direct or indirect mechanism. In the future, Il-6 may be targeted therapeutically to ameliorate symptoms of mucositis.
A Cre-amplifier to generate and detect genetic mosaicsin vivo
Authors: Trovato Francesco , Parra Riccardo , Pracucci Enrico , Landi Silvia , Cozzolino Olga , Nardi Gabriele , Cruciani Federica , Mosti Laura , Cwetsch Andrzej , Cancedda Laura , Gritti Laura , Sala Carlo , Verpelli Chiara , Maset Andrea , Lodovichi Claudia , Ratto Gian Michele 
Published: July 2019

AbstractCre-Lox manipulation is the gold standard for cell-specific expression or knockout of selected genes. However, it is not unusual to deal with conditions of low Cre expression or transient activation, which can often go undetected by conventional Cre-reporters. We designed Beatrix, a general-purpose tool specifically devised to amplify weak Cre recombinase activity, and we used it to develop a powerful approach for thein vivogeneration and detection of sparse mosaics of mutant and wild type cells.
GATA2 Expression by Intima-Infiltrating Macrophages Drives Early Atheroma Formation
Authors: Yin Charles , Vrieze Angela M. , Akingbasote James , Pawlak Emily N. , Jacob Rajesh Abraham , Hu Jonathan , Sharma Neha , Dikeakos Jimmy D. , Barra Lillian , Nagpal A. Dave , Heit Bryan 
Published: July 2019

AbstractAberrant macrophage polarization is a major contributor to the onset and progression of atherosclerosis. Despite this, macrophage polarization during in early stages of human atherosclerotic disease is poorly understood. Using transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions, we have identified a unique gene expression profile dissimilar to that observed in later stages of disease that is characterized by upregulation of the hematopoietic transcription factor GATA2. GATA2 overexpressionin vitrorecapitulated defects observed in patient macrophages, including deficiencies in the uptake and processing of apoptotic cells, and in the catalysis of atherogenic protein modifications, with GATA2 knockdown abrogating these defects. Our data describe a previously unreported macrophage differentiation state present in early atheroma formation and identifies GATA2 as a driver of macrophage functional defects during the early stages of atherosclerosis in humans.
Integrated biorefinery fromArthrospira platensisbiomass as feedstock for bioethanol and lactic acid production
Authors: Esquivel-Hernández Diego A. , Pennacchio Anna , Saldivar Roberto Parra , Faraco Vincenza 
Published: July 2019

AbstractAn integrated biorefinery for ethanol and lactic acid production from the biomass of cyanobacteriumArthrospira platensiswas investigated. Different pretreatments consisting of supercritical fluid extraction (SFE) and microwave assisted extraction (MAE) with non-polar (MAE-NPS) and polar solvents (MAE-PS) were tested on cyanobacterial biomass to obtain bioactive metabolites and the resulting residual biomass was used as a substrate for fermentation withSaccharomyces cerevisiaeLPB-287 andLactobacillus acidophilusATCC 43121 to produce ethanol and lactic acid, respectively. The maximum concentrations achieved in our processes were 3.02±0.07 g/L of ethanol by the MAE-NPS process at 120 rpm 30 °C, and 9.67±0.05 g/L of lactic acid by the SFE process at 120 rpm 37 °C. Our results suggest that the proposed approach can be successfully applied in bioactive metabolites extraction and subsequently in the production of Ethanol and Lactic acid fromA. platensisdepleted biomass.
Extending site-based observations to predict the spatial patterns of vegetation structure and composition
Authors: McNellie Megan J , Oliver Ian , Ferrier Simon , Newell Graeme , Manion Glenn , Griffioen Peter , White Matt , Koen Terry , Somerville Michael , Gibbons Philip 
Published: July 2019

AbstractContextConservation planning and land management are inherently spatial processes that are most effective when implemented over large areas.ObjectivesOur objectives were to (i) use existing plot data to aggregate species inventories to growth forms and derive indicators of vegetation structure and composition and ii) generate spatially-explicit, continuous, landscape scaled models of these discrete vegetation indicators, accompanied by maps of model uncertainty.MethodUsing a case study from New South Wales, Australia, we aggregated floristic observations from 7234 sites into growth forms. We trained ensembles of artificial neural networks (ANN) to predict the distribution of these indicators over a broad region covering 11.5 million hectares. Importantly, we show spatially explicit models of uncertainty so that end-users have a tangible and transparent means of assessing models.ResultsOur key findings were firstly, widely available site-based floristic records can be used to derive aggregated indicators of the structure and composition of plant growth forms. Secondly, ANNs are a powerful method to predict continuous patterns in complex, non-linear data (Pearson’s correlation coefficient 0.83 (total native vegetation cover) to 0.42 (forb cover)). Thirdly, maps of the standardised residual error give insight into model performance and provide an assessment of model uncertainty in specific locations.ConclusionsSpatially explicit, continuous representations of vegetation composition and structural complexity can add considerable value to conventional maps of vegetation extent or community type. This application has the potential to enhance the capacity for conservation planners, landscape managers and policy-makers to make informed decisions across landscape and regional scales.