bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary roles for ventral pallidum cell types and their projections in relapse
Authors: Prasad Asheeta A. , Xie Caroline , Chaichim Chanchanok , Killcross Simon , Power John M. , McNally Gavan P. 
Published: January 2019

AbstractVentral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking but how this role relates to different VP cell types and their projections is poorly understood. Using male rats, we show how different forms of relapse to alcohol-seeking are assembled from VP cell types and their projections to lateral hypothalamus (LH) and ventral tegmental area (VTA). First, we used RNAScope in situ hybridization to characterize activity of different VP cell types during relapse to alcohol-seeking provoked by renewal (context-induced reinstatement). We found that VP Gad1 and parvalbumin (PV), but not vGlut2, neurons show relapse-associated changes in c-Fos expression. Next, we used retrograde tracing, chemogenetic, optogenetic, and electrophysiological approaches to study the roles of VPGad1 and VPPV neurons in relapse. We show that VPGad1 neurons contribute to contextual control over relapse (renewal), but not to relapse during reacquisition, via projections to LH where they converge with ventral striatal inputs onto LHGad1 neurons. This convergence of striatopallidal inputs at the level of individual LHGad1 neurons may be critical to balancing propensity for relapse versus abstinence. In contrast, VPPV neurons contribute to relapse during both renewal and reacquisition via projections to VTA but not LH. These findings show complementary roles for different VP cell types and their projections in relapse. VPGad1 neurons control relapse during renewal via projections to LH whereas VPPV neurons control relapse during both renewal and reacquisition via projections to VTA. Targeting these different pathways may provide tailored interventions for different forms of relapse.
Heterologous expression of Stlac2, a laccase isozyme of Setosphearia turcica, and the ability of decolorization of malachite green
Authors: Liu Ning , Shen Shen , Jia Hui , Yang Beibei , Guo Xiaoyue , Si Helong , Cao Zhiyan , Dong Jingao 
Published: January 2019

AbstractLaccases can catalyze monoelectronic oxidation and have shown to have an increasing value in industrial application. In this study, as identified by Native-PAGE and ESI-MS/MS, ascomycetous fungus Setosphaeria turcica produced three laccase isozymes: Stlac1, Stlac2, and Stlac6. Stlac2 was heterologously expressed in both eukaryotic and prokaryotic expression systems. The eukaryotic recombinant Stlac2 expressed in Pichia pastoris was inactive, and also showed a higher molecular weight than predicted because of glycosylation. The depression of laccase activity was attributable to the incorrect glycosylation at Asn97. Stlac2 expressed in Escherichia coli and after being renaturated from the inclusion body, the recombinant Stlac2 exhibited activity of 28.23 U/mg with 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. The highest activity was observed at pH of 4.5 and the temperature of 60 °C. The activity of recombinant Stlac2 was inhibited by 10 mM Na+, Mg2+, Ca2+, Mn2+, and increased by 10 mM of Fe3+ with a relatively activity of 315% compared with no addition. Cu2+ did not affect enzyme activity. Recombinant Stlac2 was capable of decolorizing 67.08% of 20 mg/L malachite green in 15 min without any mediators. It is suggested that Stlac2 has potential industrial applications.ImportanceSetosphaeria turcica, an ascomycetous fungus causes northern corn leaf blight, product three laccase isozymes identified by Native-PAGE and ESI-MS/MS. The major expression laccase gene StLAC2 was expression in both eukaryotic and prokaryotic expression systems, which found incorrect glycosylation at Asn97 may result in the depression of laccase activity. The heterologous laccase Stlac2 decolorize organic dye malachite green, which had a potential industrial application.
GIGI2: A Fast Approach for Parallel Genotype Imputation in Large Pedigrees
Authors: Ullah Ehsan , Kunji Khalid , Wijsman Ellen M. , Saad Mohamad 
Published: January 2019

AbstractMotivationImputation of untyped SNPs has become important in Genome-wide Association Studies (GWAS). There has also been a trend towards analyzing rare variants, driven by the decrease of genome sequencing costs. Rare variants are enriched in pedigrees that have many cases or extreme phenotypes. This is especially the case for large pedigrees, which makes family-based designs ideal to detect rare variants associated with complex traits. The costs of performing relatively large family-based GWAS can be significantly reduced by fully sequencing only a fraction of the pedigree and performing imputation on the remaining subjects. The program GIGI can efficiently perform imputation in large pedigrees but can be time consuming. Here, we implement GIGI’s imputation approach in a new program, GIGI2, which performs imputation with computational time reduced by at least 25x on one thread and 120x on eight threads. The memory usage of GIGI2 is reduced by at least 30x. This reduction is achieved by implementing better memory layout and a better algorithm for solving the Identity by Descent graphs, as well as with additional features, including multithreading. We also make GIGI2 available as a webserver based on the same framework as the Michigan Imputation Server.AvailabilityGIGI2 is freely available online at https://cse-git.qcri.org/eullah/GIGI2 and the websever is at https://imputation.qcri.org/Contactmsaad@hbku.edu.qa
SPIKEPIPE: A metagenomic pipeline for the accurate quantification of eukaryotic species occurrences and abundances using DNA barcodes or mitogenomes
Authors: Ji Yinqiu , Huotari Tea , Roslin Tomas , Schmidt Niels Martin , Wang Jiaxin , Yu Douglas W. , Ovaskainen Otso 
Published: January 2019

AbstractThe accurate quantification of eukaryotic species abundances from bulk samples remains a key challenge for community description and environmental biomonitoring. We resolve this challenge by combining shotgun sequencing, mapping to reference DNA barcodes or to mitogenomes, and three correction factors: (1) a percent-coverage threshold to filter out false positives, (2) an internal-standard DNA spike-in to correct for stochasticity during sequencing, and (3) technical replicates to correct for stochasticity across sequencing runs. This pipeline achieves a strikingly high accuracy of intraspecific abundance estimates from samples of known composition (mapping to barcodes R2=0.93, mitogenomes R2=0.95) and a high repeatability across environmental-sample replicates (barcodes R2=0.94, mitogenomes R2=0.93). As proof of concept, we sequence arthropod samples from the High Arctic systematically collected over 17 years, detecting changes in species richness, abundance, and phenology using either barcodes or mitogenomes. SPIKEPIPE provides cost-efficient and reliable quantification of eukaryotic communities, with direct application to environmental biomonitoring.Statement of authorshipNMS has been involved in running the BioBasis sampling program for more than twenty years. TR, NMS, DWY, and OO conceived the study and its design. TH led the work in generating all the DNA samples and YJ led the work in assembling and annotating the mitogenomes for the mitochondrial genome reference database. TH led the work in generating the mock communities and bulk samples, with contributions from YJ and JW. YJ and DWY developed the molecular and bioinformatic methods. OO led the modelling of the data. TR and OO wrote the first draft of the manuscript, and all authors contributed substantially to its further improvement.Data accessibility statementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository (Dryad), and the data DOI will be included at the end of the article. The bioinformatic and R scripts and associated data tables will also be made available on github.com.
Bayesian Tip-dated Phylogenetics: Topological Effects, Stratigraphic Fit and the Early Evolution of Mammals
Authors: King Benedict , Beck Robin 
Published: January 2019

ABSTRACTThe incorporation of stratigraphic data into phylogenetic analysis has a long history of debate, but is not currently standard practice for palaeontologists. Bayesian tip-dating (or morphological clock) phylogenetic methods have returned these arguments to the spotlight, but how tip-dating affects the recovery of evolutionary relationships has yet to be fully explored. Here we show, through analysis of several datasets with multiple phylogenetic methods, that topologies produced by tip-dating are outliers when compared to topologies produced by parsimony and undated Bayesian methods, which retrieve broadly similar trees. Unsurprisingly, trees recovered by tip-dating have better fit to stratigraphy than trees recovered by other methods, due to trees with better stratigraphic fit being assigned a higher prior probability. Differences in stratigraphic fit and tree topology between tip-dating and other methods appear to be concentrated in parts of the tree with weaker character signal and a stronger influence of the prior, as shown by successive deletion of the most incomplete taxa from a sauropod dataset. Tip-dating applied to Mesozoic mammals firmly rejects a monophyletic Allotheria, and strongly supports diphyly of haramiyidans, with the late TriassicHaramiyaviaandThomasiaforming a clade with tritylodontids, which is distant from the middle Jurassic euharamiyidans. This result is not sensitive to the controversial age of the eutherianJuramaia. A Test of the age ofJuramaiausing a less restrictive prior reveals strong support from the data for an Early Cretaceous age. Our results suggest that tip-dating incorporates stratigraphic data in an intuitive way, with good stratigraphic fit a prior expectation that can be overturned by strong evidence from character data.
Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina
Authors: Joseph Aby , Guevara–Torres Andrés , Schallek Jesse B. 
Published: January 2019

Impact StatementUsing a specialized camera that corrects for eye blur, millions of single blood cells are imaged and their speed measured, as they travel through the largest-to-smallest vessels of the retina.AbstractTissue light scatter limits the visualization of the microvascular network deep inside the living mammal. The transparency of the mammalian eye provides a noninvasive view of the microvessels of the retina, a part of the central nervous system. Despite its clarity, imperfections in the optics of the eye blur microscopic retinal capillaries, and single blood cells flowing within. This limits early evaluation of microvascular diseases that originate in capillaries. To break this barrier, we use adaptive optics to noninvasively measure single–cell blood flow, in one of the most widely used research animals: the C57BL/6J mouse. Flow ranged four orders of magnitude (0.0002–1.55 µL min−1) across the full spectrum of retinal vessel diameters (3.2–45.8 µm), without requiring surgery or contrast dye. Here we describe the data collection approach using adaptive optics and provide an analysis pipeline that can measure millions of blood cell speeds automatically.
ABCDE approach to victims by lifeguards: how do they manage a critical patient? A cross sectional simulation study
Authors: Fernández-Méndez Felipe , Otero-Agra Martín , Abelairas-Gómez Cristian , Saez-Gallego Nieves Maria , Rodríguez-Núñez Antonio , Barcala-Furelos Roberto 
Published: January 2019

AbstractIntroductionDecision-making in emergencies is a multifactorial process based on the rescuer, patient, setting and resources. The eye-tracking system is a proven method for assessing decision-making process that has been used in different fields of science. Our aim was to evaluate the lifeguards' capacity to perform the ABCDE (Airway-Breathing-Circulation-Dissability-Exposure) approach when facing a simulated critically ill-drowned victim.MethodsA cross sectional simulation study was designed to assess the skills and sequence of the ABCDE approach by 20 professional lifeguards. They had to assess a victim and act according to his/her clinical status following the ABCDE primary assessment approach. Two kind of variables were recorder: those related to quality of each step of the ABCDE approach; visual behaviour using a portable eye-movement system. The eye-tracking system was the Mobile Eye system (Bedford, USA).ResultsNone of the study participants was able to complete correctly the ABCDE approach. Lifeguards spent more time in the Circulation step: Airway (15.5±11.1 s), Breathing (25.1±21.1 s), Circulation (44.6±29.5 s), Disability (38.5±0.7 s). Participants spent more time in viewpoints considered as important (65.5±17.4 s) compared with secondary ones (34.6±17.4 s, p = 0.008). This also was represented in the percentage of visual fixations (fixations in important viewpoints: 63.36±15.06; fixation in secondary viewpoints: 36.64±15.06).ConclusionProfessional lifeguards failed to fully perform the ABCDE sequence. Evaluation by experts with the help of eye-tracking technology detected lifeguards' limitations in the assessment and treatment of an eventual critically ill victim. Such deficits should be considered in the design and implementation of lifeguards’ training programmes.
Mating Induces Switch From Hormone-Dependent to – Independent Steroid Receptor-Mediated Growth in Drosophila Prostate-Like Cells
Authors: Leiblich Aaron , Hellberg Josephine E. E. U. , Sekar Aashika , Gandy Carina , Redhai Siamak , Wainwright Mark , Marie Pauline , Goberdhan Deborah C. I. , Hamdy Freddie C. , Wilson Clive 
Published: January 2019

AbstractMale reproductive glands like the mammalian prostate and the paired Drosophila melanogaster accessory glands secrete seminal fluid components that enhance fecundity. In humans, the prostate grows throughout adult life, stimulated by environmentally regulated endocrine and local androgens. We previously showed that in each fly accessory gland, secondary cells (SCs) and their nuclei also grow in adults, a process enhanced by mating and controlled by bone morphogenetic protein (BMP) signalling. Here we demonstrate that BMP-mediated SC growth is dependent on the receptor for the developmental steroid, ecdysone, whose concentration reflects socio-sexual experience in adults. BMP signalling regulates ecdysone receptor (EcR) levels post-transcriptionally, partly via EcR’s N-terminus. Nuclear growth in virgin males is ecdysone-dependent. However, mating activates genome endoreplication to drive additional BMP-mediated nuclear growth via a cell type-specific form of hormone-independent EcR signalling. In virgin males with low ecdysone levels, this mechanism ensures resources are conserved. However, by switching to hormone-independence after mating, this control is overridden to hyper-activate growth of secretory secondary cells. Our data suggest parallels between this physiological, behaviour-induced switch and altered pathological signalling associated with prostate cancer progression.
Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine againstCryptococcus neoformans var. grubii’sheat shock 70KDa protein
Authors: Elhassan Reham M. , Alsony Nagla M. , Othman Khadeejah M. , Izz-Aldin Duaa T. , Alhaj Tamadour A. , Ali Abdelrahman A. , Abashir Lena A. , Ahmed Omar H. , Hassan Mohammed A. 
Published: January 2019

AbstractIntroductionCryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and none-HIV carriers with 99% and 95% respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multi-drug resistant organism, and the scarcity of FDA authorized vaccines, where the hallmark in the present days. This study was undertaken to design a reliable multi-epitope peptide vaccine against highly conserved immunodominant heat shock 70KDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing computational vaccinology approach.Materials and MethodsA total of 38 Sequences of Cryptococcus neoformans var. grubii’s heat shock 70KDa protein were retrieved from NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at Immune Epitope Database (IEDB) to discriminate the most promising T-cell and B-cell epitopes. Then the proposed epitopes were subjected to Population coverage analysis tool to compute global population’s coverage. Finally, the projected epitopes were ranked based on their scores and binding modes through using Moe 2007 program.Outstanding Results and ConclusionOur prime vaccine candidate was a putative ten promising epitopes (ANYVQASEK, NYVQASEK, KSVEKPAS, TPQQPPAQ, YVYDTRGKL, FYRQGAFEL, FTQLVAAYL, FFGGKVLNF, FDYALVQHF, and FINAQLVDV). Together, these epitopes are forecasted to trigger T lymphocytes, B lymphocytes, and immunological memory with overall population coverage above 90%. Accordingly, our in silico vaccine is expected to be the future multi-epitope peptide vaccine against Cryptococcus neoformans var. grubii’s heat shock 70KDa protein that covers a significant figure of the entire world citizens. Therefore, there is a definite need for experimental validation for the carefully chosen vaccine candidates in vitro and in vivo to fortify their antigenic and immunogenic potentials. Additionally, further computational studies are needed to be conducted in pathogens-derived Heat shock 70KDa protein family, as it believed to find universal epitopes that might be overlapped with other pathogens-derived Hsp70.
Controlling gene activation by enhancers through a drug-inducible topological insulator
Authors: Tsujimura Taro , Takase Osamu , Yoshikawa Masahiro , Sano Etsuko , Hayashi Matsuhiko , Hoshi Kazuto , Takato Tsuyoshi , Toyoda Atsushi , Okano Hideyuki , Hishikawa Keiichi 
Published: January 2019

AbstractWhile regulation of gene-enhancer interaction is better understood, its application remains limited. Here, we reconstituted arrays of CTCF binding sites and devised a synthetic topological insulator with tetO for chromatin-engineering (STITCH). By coupling STITCH with tetR linked to the KRAB domain to induce heterochromatin and disable the insulation, we developed a drug-inducible system to control gene activation by enhancers. We applied this to dissect MYC regulation in human pluripotent stem cells. Insertion of STITCH between MYC and the enhancer down-regulated MYC and affected its target transcriptome. Progressive mutagenesis of STITCH led to preferential escalation of the gene-enhancer interaction, corroborating the strong insulation ability of STITCH. The STITCH insertion altered epigenetic states around MYC. Time-course analysis by drug induction uncovered deposition and removal of H3K27me3 repressive marks follows and reflects, but does not precede and determine, the expression change. Thus the tool provided important insights in gene regulation, demonstrating its potency.
The determinants of genetic diversity in butterflies – Lewontin’s paradox revisited
Authors: Mackintosh Alexander , Laetsch Dominik R. , Hayward Alexander , Waterfall Martin , Vila Roger , Lohse Konrad 
Published: January 2019

AbstractUnder the neutral theory genetic diversity is expected to be a simple function of population size. However, comparative studies have consistently failed to find any strong correlation between measures of census population size and genetic diversity. Instead, a recent comparative study across several animal phyla identified propagule size as the strongest predictor of genetic diversity, suggesting that r-strategists that produce many offspring but invest little in each, have greater long-term effective population sizes. We present a comparison of genome-wide levels of genetic diversity across 38 species of European butterflies (Papilionoidea). We show that across butterflies, genetic diversity varies over an order of magnitude and that this variation cannot be explained by differences in abundance, fecundity, host plant use or geographic range. Instead, we find that genetic diversity is negatively correlated with body size and positively with the length of the genetic map. This suggests that variation in genetic diversity is determined both by fluctuation inNeand the effect of selection on linked neutral sites.
HOPS: Automated detection and authentication of pathogen DNA in archaeological remains
Authors: Hübler Ron , Key Felix M. , Warinner Christina , Bos Kirsten I. , Krause Johannes , Herbig Alexander 
Published: January 2019

AbstractHigh-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present day environmental or clinical samples, but can also be fruitfully applied to molecular data from archaeological remains (ancient DNA), and a focus on ancient bacteria can provide valuable information on the long-term evolutionary relationship between hosts and their pathogens. Here we present HOPS (HeuristicOperations forPathogenScreening), an automated bacterial screening pipeline for ancient DNA sequence data that provides straightforward and reproducible information on species identification and authenticity. HOPS provides a versatile and fast pipeline for high-throughput screening of bacterial DNA from archaeological material to identify candidates for subsequent genomic-level analyses.
PGxCorpus: a Manually Annotated Corpus for Pharmacogenomics
Authors: Legrand Joël , Gogdemir Romain , Bousquet Cédric , Dalleau Kevin , Devignes Marie-Dominique , Digan William , Lee Chia-Ju , Ndiaye Ndeye-Coumba , Petitpain Nadine , Ringot Patrice , Smaïl-Tabbone Malika , Toussaint Yannick , Coulet Adrien 
Published: January 2019

AbstractPharmacogenomics (PGx) studies how individual gene variations impact drug response phenotypes, which makes knowledge related to PGx a key component towards precision medicine. A significant part of the state-of-the-art knowledge in PGx is accumulated in scientific publications, where it is hardly usable to humans or software. Natural language processing techniques have been developed and are indeed employed for guiding experts curating this amount of knowledge. But, existing works are limited by the absence of high quality annotated corpora focusing on the domain. This absence restricts in particular the use of supervised machine learning approaches. This article introduces PGxCorpus, a manually annotated corpus, designed for the automatic extraction of PGx relationships from text. It comprises 945 sentences from 911 PubMed abstracts, annotated with PGx entities of interest (mainly genes variations, gene, drugs and phenotypes), and relationships between those. We present in this article the method used to annotate consistently texts, and a baseline experiment that illustrates how this resource may be leveraged to synthesize and summarize PGx knowledge.