bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral and Virucidal activities of sulphated polysaccharides against Japanese Encephalitis Virus
Authors: Rothan Hussin A. , Yusof Rohana 
Published: February 2020

AbstractBackgroundJapanese encephalitis virus (JEV), a member of the family Flaviviridae, causes severe neurological disorders in humans. JEV infections represent one of the most widely spread mosquito-borne diseases, and therefore, it has been considered as an endemic disease. An effective antiviral drug is still unavailable to treat JEV, and current drugs only provide supportive treatment to alleviate the symptoms and stabilize patients’ conditions. This study was designed to evaluate the antiviral activity of the sulphated polysaccharides “Carrageenan,” a linear sulphated polysaccharide that is extracted from red edible seaweeds against JEV replication in vitro.Methods and ResultsViral inactivation, attachment, and post-infection assays were used to determine the mode of inhibition of Carrageenan. Virus titters after each application were evaluated by plaque formation assay. MTT assay was used to determine the 50% cytotoxic concentration (CC50), and ELISA-like cell-based assay and immunostaining and immunostaining techniques were used to evaluate the 50% effective concentration (EC50). This study showed that Carrageenan inhibited JEV at an EC50 of 15 μg/mL in a dose-dependent manner with CC50 more than 200 μg/mL in healthy human liver cells (WRL68). The mode of inhibition assay showed that the antiviral effects of Carrageenan are mainly due to their ability to inhibit the early stages of virus infection such as the viral attachment and the cellular entry stages.ConclusionOur investigation showed that Carrageenan could be considered as a potent antiviral agent to JEV infection. Further experimental and clinical studies are needed to investigate the potential applications of Carrageenan for clinical intervention against JEV infection.
iGenomics: Comprehensive DNA Sequence Analysis on your Smartphone
Authors: Palatnick Aspyn , Zhou Bin , Ghedin Elodie , Schatz Michael C. 
Published: February 2020

AbstractFollowing the miniaturization of integrated circuitry and other computer hardware over the past several decades, DNA sequencing is following a similar path. Leading this trend is the Oxford Nanopore sequencing platform, which currently offers the hand-held MinION instrument and even smaller instruments on the near horizon. This technology has been used in several important applications, including the analysis of genomes of major pathogens in remote stations around the world. However, despite the simplicity of the sequencer, an equally simple and portable analysis platform is not yet available.iGenomics is the first comprehensive mobile genome analysis application, with capabilities to align reads, call variants, and visualize the results entirely on an iOS device. Implemented in Objective-C using the FM-index, banded dynamic programming, and other high-performance bioinformatics techniques, iGenomics is optimized to run in a mobile environment. We benchmark iGenomics using a variety of real and simulated Nanopore sequencing datasets and show that iGenomics has performance comparable to the popular BWA-MEM/Samtools/IGV suite, without needing a laptop or server cluster. iGenomics is available open-source (https://github.com/stuckinaboot/iGenomics) and for free on Apple’s App Store (https://apps.apple.com/us/app/igenomics-mobile-dna-analysis/id1495719841).
A footprint of plant eco-geographic adaptation on the composition of the barley rhizosphere bacterial microbiota
Authors: Terrazas Rodrigo Alegria , Balbirnie-Cumming Katharin , Morris Jenny , Hedley Pete E , Russell Joanne , Paterson Eric , Baggs Elizabeth M , Fridman Eyal , Bulgarelli Davide 
Published: February 2020

AbstractThe microbiota thriving in the rhizosphere, the thin layer of soil surrounding plant roots, plays a critical role in plant’s adaptation to the environment. Domestication and breeding selection have progressively differentiated the microbiota of modern crops from the ones of their wild ancestors. However, the impact of eco-geographical constraints faced by domesticated plants and crop wild relatives on recruitment and maintenance of the rhizosphere microbiota remains to be fully elucidated. Here we performed a comparative 16S rRNA gene survey of the rhizosphere of 4 domesticated and 20 wild barley (Hordeum vulgare) genotypes grown in an agricultural soil under controlled environmental conditions. We demonstrated the enrichment of individual bacteria mirrored the distinct eco-geographical constraints faced by their host plants. Unexpectedly, Elite varieties exerted a stronger genotype effect on the rhizosphere microbiota when compared with wild barley genotypes adapted to desert environments with a preferential enrichment for members of Actinobacteria. Finally, in wild barley genotypes, we discovered a limited, but significant, correlation between microbiota diversity and host genomic diversity. Our results revealed a footprint of the host’s adaptation to the environment on the assembly of the bacteria thriving at the root-soil interface. In the tested conditions, this recruitment cue layered atop of the distinct evolutionary trajectories of wild and domesticated plants and, at least in part, is encoded by the barley genome. This knowledge will be critical to design experimental approaches aimed at elucidating the recruitment cues of the barley microbiota across a range of soil types.
Next-generation cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity
Authors: Yu Yi , Leete Thomas , Born David A. , Young Lauren , Barrera Luis A. , Lee Seung-Joo , Rees Holly A. , Ciaramella Giuseppe , Gaudelli Nicole M. 
Published: February 2020

Abstract/introductory paragraphCytosine base editors (CBEs) are molecular machines which enable efficient and programmable reversion of T•A to C•G point mutations in the human genome without induction of DNA double strand breaks1, 2. Recently, the foundational cytosine base editor (CBE) ‘BE3’, containing rAPOBEC1, was reported to induce unguided, genomic DNA3, 4and cellular RNA5cytosine deamination when expressed in living cells. To mitigate spurious off-target events, we developed a sensitive, high-throughput cellular assay to select next-generation CBEs that display reduced spurious deamination profiles relative to rAPOBEC1-based CBEs, whilst maintaining equivalent or superior on-target editing frequencies. We screened 153 CBEs containing cytidine deaminase enzymes with diverse sequences and identified four novel CBEs with the most promising on/off target ratios. These spurious-deamination-minimized CBEs (BE4 with either RrA3F, AmAPOBEC1, SsAPOBEC3B, or PpAPOBEC1) were further optimized for superior on- and off-target DNA editing profiles through structure-guided mutagenesis of the deaminase domain. These next-generation CBEs display comparable overall DNA on-target editing frequencies, whilst eliciting a 10- to 49-fold reduction in C-to-U edits in the transcriptome of treated cells, and up to a 33-fold overall reduction in unguided off-target DNA deamination relative to BE4 containing rAPOBEC1. Taken together, these next-generation CBEs represent a new collection of base editing tools for applications in which minimization of spurious deamination is desirable and high on-target activity is required.
The genome sequence of the Jean-Talon strain, an archeological tetraploid beer yeast from Québec
Authors: Fijarczyk Anna , Hénault Mathieu , Marsit Souhir , Charron Guillaume , Fischborn Tobias , Nicole-Labrie Luc , Landry Christian R 
Published: February 2020

AbstractThe genome sequences of archeological yeast isolates can reveal insights about the history of human baking, brewing and winemaking activities and migration around the globe. A yeast strain called Jean-Talon was recently isolated from the vaults of the Intendant’s Palace of Nouvelle France on a historical site in Québec City. This site has been occupied by various breweries, starting from the end of the 17th century and until the middle of the 20th century. We sequenced the genome of the Jean-Talon strain with short and long reads and reanalyzed the genomes of hundreds of yeast strains to identify its species of origin and determine how it relates to other domesticated and wild strains. The Jean-Talon strain is a tetraploid strain with numerous aneuploidies, is partially sterile and most closely related to beer strains from the beer and bakery genetic groups and industrial strains from the United Kingdom and Belgium. We conclude from this that the Jean-Talon strain most likely derives from recent brewing activities that took place in the same location and not from wild yeast that could have been domesticated by the original brewers of the Nouvelle France on the site.
Kupffer Cell Release of Platelet Activating Factor Drives Dose Limiting Toxicities of Nucleic Acid Nanocarriers
Authors: Jackson Meredith A. , Patel Shrusti S. , Yu Fang , Cottam Matthew A. , Glass Evan B. , Dollinger Bryan R. , Hoogenboezem Ella N. , Patil Prarthana , Liu Danielle D. , Kelly Isom B. , Bedingfield Sean K. , King Allyson R. , Miles Rachel E. , Hasty Alyssa M. , Giorgio Todd D. , Duvall Craig L. 
Published: February 2020

AbstractIn vivonanocarrier-associated toxicity is a significant and poorly understood hurdle to clinical translation of siRNA nanomedicines. In this work, we demonstrate that platelet activating factor (PAF), an inflammatory lipid mediator, plays a key role in nanocarrier-associated toxicities, and that prophylactic inhibition of the PAF receptor (PAFR) completely prevents these toxicities. High-dose intravenous injection of siRNA-polymer nano-complexes (si-NPs) elicited acute, shock-like symptoms (vasodilation and vascular leak) in mice and caused a three-fold increase in blood PAF levels. PAFR inhibition completely prevented these toxicities, indicating PAF activity is a primary driver of systemic si-NP toxicity. Pre-treatment with clodronate liposomes fully abrogated si-NP-associated increases in blood PAF and consequent toxicities, suggesting that nanoparticle uptake by Kupffer macrophages is the source of PAF. Assessment of varied si-NP chemistries further confirmed that toxicity level correlated to relative uptake of the carrier by liver Kupffer cells and that this toxicity mechanism is dependent on the endosome disruptive function of the carrier. Finally, the PAF toxicity mechanism was shown to be generalizable to commercial delivery reagentin vivo-jetPEI®and an MC3 lipid nanoparticle formulated to match an FDA-approved siRNA nanomedicine. Greater sensitivity to the PAF mechanism occurs in 4T1 tumor-bearing mice, a mammary tumor model known to exhibit increased circulating leukocytes and potential to respond to inflammatory insult. These results establish Kupffer cell release of PAF as a key mediator ofin vivonucleic acid nanocarrier toxicity and identify PAFR inhibition as an effective prophylactic strategy to increase maximum tolerated dose and reduce nanocarrier-associated adverse events.SignificanceNon-viral nucleic acid nanocarriers can enablein vivogene therapy, but their potential interaction with innate immune cells can cause dose-limiting toxicities. Nanoparticle toxicities are currently poorly understood, making it difficult to identify relevant design criteria for maximizing nanoparticle safety. This work connects nanoparticle-associated toxicities to the release of platelet activating factor (PAF) by liver Kupffer cells. Small molecule inhibition of the PAF receptor (PAFR) completely prevents severe adverse events associated with high doses of multiple polymer-based formulations and a lipid nanoparticle matching the composition of the first clinically-approved siRNA nanomedicine. This study identifies PAF as a toxicity biomarker for future nanomedicine discovery programs. Further, PAFR inhibition should be explored as a strategy to expand the therapeutic index of nanomedicines.
Amyloid fibril structure of islet amyloid polypeptide by cryo-electron microscopy reveals similarities with amyloid beta
Authors: Röder Christine , Kupreichyk Tatsiana , Gremer Lothar , Schäfer Luisa U. , Pothula Karunakar R. , Ravelli Raimond B. G. , Willbold Dieter , Hoyer Wolfgang , Schröder Gunnar F. 
Published: February 2020

AbstractA critical role of the hormone islet amyloid polypeptide (IAPP) is vividly discussed for Type 2 Diabetes (T2D), where amyloid deposits in pancreatic islets consisting of fibrillar IAPP have been associated with beta cell loss. Here, we applied cryo-electron microscopy to elucidate the structure of IAPP fibrils prepared at physiological pH and reconstructed densities of three dominant polymorphs. An atomic model of the main polymorph comprising residues 13 – 37 in a density map of 4.2 Å resolution reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, which is essential for IAPP amyloidogenicity, forms the protofilament interface together with tyrosine 37 and the amidated C-terminus. The main IAPP fibril polymorph resembles polymorphs of the Alzheimer disease (AD)-associated amyloid-β peptide (Aβ), which is striking in light of the epidemiological link between T2D and AD and reports on IAPP-Aβ cross-seedingin vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism S20G with the early-onset AD Arctic mutation E22G of Aβ, rationalize previous data on IAPP fibrils, help to elucidate mechanisms of amyloid formation and toxicity, and support the design of fibril growth inhibitors as well as imaging probes for early detection of IAPP fibrils.
Co-transcriptional splicing regulates 3’ end cleavage during mammalian erythropoiesis
Authors: Reimer Kirsten A. , Mimoso Claudia , Adelman Karen , Neugebauer Karla M. 
Published: February 2020

ABSTRACTPre-mRNA processing steps are tightly coordinated with transcription in many organisms. To determine how co-transcriptional splicing is integrated with transcription elongation and 3’ end formation in mammalian cells, we performed long-read sequencing of individual nascent RNAs and PRO-seq during mouse erythropoiesis. Splicing was not accompanied by transcriptional pausing and was detected when RNA polymerase II (Pol II) was within 75 – 300 nucleotides of 3’ splice sites (3’SSs), often during transcription of the downstream exon. Interestingly, several hundred introns displayed abundant splicing intermediates, suggesting that splicing delays can take place between the two catalytic steps. Overall, splicing efficiencies were correlated among introns within the same transcript, and intron retention was associated with inefficient 3’ end cleavage. Remarkably, a thalassemia patient-derived mutation introducing a cryptic 3’SS improves both splicing and 3’ end cleavage of individual β-globin transcripts, demonstrating functional coupling between the two co-transcriptional processes as a determinant of productive gene output.
Combination of antifungal drugs and protease inhibitors preventCandida albicansbiofilm formation and disrupt mature biofilms
Authors: Lohse Matthew B. , Gulati Megha , Craik Charles S. , Johnson Alexander D. , Nobile Clarissa J. 
Published: February 2020

AbstractBiofilms formed by the fungal pathogenCandida albicansare resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to preventC. albicansbiofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents forCandidainfections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment ofC. albicansbiofilm infections.ImportanceCandida albicansis one of the most common pathogens of humans.C. albicansforms biofilms, structured communities of cells several hundred microns thick, on both biotic and abiotic surfaces. These biofilms are typically resistant to antifungal drugs at the concentrations that are normally effective against free-floating cells, thus requiring treatment with higher drug concentrations that often have significant side effects. Here, we show that certain combinations of existing antifungal agents with protease inhibitors, including several drugs already commonly used to treat HIV patients, are effective at inhibiting biofilm formation byC. albicansand/or at disrupting matureC. albicansbiofilms.
Metagenomic analysis of the cow, sheep, reindeer and red deer rumen
Authors: Glendinning Laura , Genç Buğra , Wallace R John , Watson Mick 
Published: February 2020

AbstractThe rumen microbiota comprises a community of microorganisms which specialise in the degradation of complex carbohydrates from plant-based feed. These microbes play a highly important role in ruminant nutrition and could also act as sources of industrially useful enzymes. In this study, we performed a metagenomic analysis of samples taken from the ruminal contents of cattle (Bos Taurus), sheep (Ovis aries), reindeer (Rangifer tarandus) and red deer (Cervus elaphus). We constructed 391 metagenome-assembled genomes originating from 16 microbial phyla. We compared our genomes to other publically available microbial genomes and found that they contained 279 novel species. We also found significant differences between the microbiota of different ruminant species in terms of the abundance of microbial taxonomies, carbohydrate-active enzyme genes and KEGG orthologs. However, we found that the vast majority of carbohydrate-active enzymes were present in all of our sample types, which may indicate that there is a core set of these enzymes which are present across ruminants and are independent of diet and environmental conditions. We present a dataset of rumen-derived genomes which in combination with other publicly-available rumen genomes can be used as a reference dataset in future metagenomic studies.Data SummaryThe paired-read fastq files supporting the conclusions of this article are available in the European Nucleotide Archive repository (https://www.ebi.ac.uk/ena/browser/view/PRJEB34458). The RUG fasta files supporting the conclusions of this article are available in the Edinburgh DataShare repository (https://doi.org/10.7488/ds/2640).
Multicultural attitudes and cultural intelligence of preschool teachers
Authors: Peköz Çağrı , Gürşimşek Ayşe Işık 
Published: February 2020

Purpose
The purpose of this paper is to investigate the preschool teachers’ cultural intelligence, their attitudes towards multicultural education and the correlation between these two variables.

Design/methodology/approach
The sample consisted of 203 preschool teachers working in preschool classes within primary schools administrated by the Ministry of Education in Turkish Republic of Northern Cyprus (TRNC). Data were collected from the teachers by cultural intelligence scale (CQS), teacher multicultural attitude survey (TMAS) and demographic information form.

Findings
The analysis revealed that cultural intelligence and attitudes towards multicultural education did not differ according to teaching experience in a foreign country. Significant differences were found in metacognition, motivation and behaviour sub-dimension scores, cultural intelligence total scores and multicultural education attitude scores because of having a friend in foreign country, cognition sub-dimension scores because of having a non-Turkish-speaking student (NTSS) in class and cultural intelligence total scores because of knowing a foreign language. Significant relation was found between cultural intelligence scores and multicultural education attitude scores of the participants.

Originality/value
Despite the increasing cultural diversity in the country, there are no official regulations or efforts to establish arrangements for multicultural education in TRNC. Thus, this research is valuable for clarifying the situation in TRNC, determining the requirements and providing insights for future scientific work and implications.
Design for maintenance: new algorithmic approach
Authors: Adjoul Oussama , Benfriha Khaled , Aoussat Améziane 
Published: February 2020

PurposeThis paper proposes a new simultaneous optimization model of the industrial systems design and maintenance. This model aims to help the designer in searching for technical solutions and the product architecture by integrating the maintenance issues from the design stage. The goal is to reduce the life-cycle cost (LCC) of the studied system.Design/methodology/approachLiterature indicates that the different approaches used in the design for maintenance (DFM) methods are limited to the simultaneous characterization of the reliability and the maintainability of a multicomponent system as well as the modeling of the dynamic maintenance. This article proposes to go further in the optimization of the product, by simultaneously characterizing the design, in terms of reliability and maintainability, as well as the dynamic planning of the maintenance operations. This combinatorial characterization is performed by a two-level hybrid algorithm based on the genetic algorithms.FindingsThe proposed tool offers, depending on the life-cycle expectation, the desired availability, the desired business model (sales or rental), simulations in terms of the LCCs, and so an optimal product architecture.Research limitations/implicationsIn this article, the term “design” is limited to reliability properties, possible redundancies, component accessibility (maintainability), and levels of monitoring information.Originality/valueThis work is distinguished by the use of a hybrid optimization algorithm (two-level computation) using genetic algorithms. The first level is to identify an optimal design configuration that takes into account the LCC criterion. The second level consists in proposing a dynamic and optimal maintenance plan based on the maintenance-free operating period (MFOP) concept that takes into account certain criteria, such as replacement costs or the reliability of the system.
When brands use CEOs and employees as spokespersons
Authors: Zeitoun Valérie , Michel Geraldine , Fleck Nathalie 
Published: February 2020

Purpose
This paper aims to clarify the persuasion mechanism of chief executive officers (CEOs) and employees as endorsers of brand advertising and helps discern consumer attitudes toward internal endorsement.

Design/methodology/approach
The exploratory character of the present research required a qualitative approach combining focus groups and face-to-face interviews considered as both meaningful and complementary.

Findings
The findings suggest that while the celebrity endorsement ensures familiarity and likability, internal endorsement supports credibility and congruity with an important role of storytelling. Moreover, employee endorsements induce an internalization process based on the real-self, while the endorser CEO induces admiration grounded in the ideal self. More fundamentally, the study reveals how the internal endorsement modifies the meaning transfer model and involves a process of meaning translation, which affects the corporate brand image rather than the product brand image.

Originality/value
The present paper reveals that CEOs and employees can be strong levers for gilding the corporate brand image compared to the celebrities who enhance the product brand image. Moreover, the authors show that the CEO is a character who can be admired without the threat of upward comparison at the opposite of celebrities. Finally, this research highlights the specific role of employees bringing authenticity because of their anchorage in real life.