bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel combination of CRISPR-based gene drives eliminates resistance and localises spread
Authors: Faber Nicky R. , McFarlane Gus R. , Gaynor R. Chris , Pocrnic Ivan , Whitelaw C. Bruce A. , Gorjanc Gregor 
Published: August 2020

AbstractInvasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR can effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.
Common Marmoset Gut Microbiome Profiles in Health and Intestinal Disease
Authors: Sheh Alexander , Artim Stephen C. , Burns Monika A. , Molina-Mora Jose Arturo , Lee Mary Anne , Dzink-Fox JoAnn , Muthupalani Sureshkumar , Fox James G. 
Published: August 2020

AbstractChronic gastrointestinal (GI) diseases are the most common diseases in captive marmosets. The gut microbiome of healthy (n=91), inflammatory bowel disease (IBD) (n=59), and duodenal ulcer/stricture (n=23) captive marmosets was characterized. Healthy marmosets exhibited a “humanized,”Bacteroidetes-dominantmicrobiome. Despite standardized conditions, cohorts subdivided intoPrevotella- andBacteroides-dominantgroups based on marmoset source. IBD was highest in aPrevotella-dominant cohort while strictures were highest in aBacteroides-dominant cohort. Stricture-associated dysbiosis was characterized byAnaerobiospirillumloss andClostridium perfringensincreases. Stricture tissue presented upregulation of lipid metabolism genes and increased abundance ofC. perfringens, a causative agent of GI diseases and intestinal strictures in humans. IBD was associated with a lowerBacteroides:P. copriratio within each source. Consistent withPrevotella-linked diseases, pro-inflammatory genes were upregulated. This report highlights the humanization of the captive marmoset microbiome and its potential as a “humanized” animal model ofC. perfringens-inducedenteritis/strictures andP. copri-associatedIBD.
Crucial Role ofSalmonellaGenomic Island 1 Master Activator in Parasitism of IncC plasmids
Authors: Durand Romain , Huguet Kévin T. , Rivard Nicolas , Carraro Nicolas , Rodrigue Sébastien , Burrus Vincent 
Published: August 2020

ABSTRACTIncC conjugative plasmids and the multiple variants ofSalmonellaGenomic Island 1 (SGI1) are two functionally interacting families of mobile genetic elements commonly associated with multidrug resistance inGammaproteobacteria. SGI1 and its siblings are specifically mobilisedin transby IncC conjugative plasmids. Conjugative transfer of IncC plasmids is activated by the plasmid-encoded master activator AcaCD. SGI1 carries five AcaCD-responsive promoters that drive the expression of genes involved in its excision, replication, and mobilisation. SGI1 encodes an AcaCD homologue, the transcriptional activator complex SgaCD (also known as FlhDCSGI1) that seems to recognise and activate the same SGI1 promoters. Here, we investigated the relevance of SgaCD in SGI1’s lifecycle. Mating assays revealed the requirement for SgaCD and its IncC-encoded counterpart AcaCD in the mobilisation of SGI1. An integrative approach combining ChIP-exo, Cappable-seq, and RNA-seq confirmed that SgaCD activates each of the 18 AcaCD-responsive promoters driving the expression of the plasmid transfer functions. A comprehensive analysis of the activity of the complete set of AcaCD-responsive promoters in both SGI1 and IncC plasmid was performed through reporter assays. qPCR and flow cytometry assays revealed that SgaCD is essential for the excision and replication of SGI1, and the destabilisation of the helper IncC plasmid.
Presence of the Hmq system and production of 4-hydroxy-3-methyl-2-alkylquinolines is heterogeneously distributed betweenBurkholderia cepaciacomplex species and more prevalent among environmental than clinical isolates
Authors: Coulon Pauline M.L. , Zlosnik James E.A. , Déziel Eric 
Published: August 2020

AbstractSomeBurkholderia cepaciacomplex (Bcc) strains have been reported to produce 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs), analogous to the 4-hydroxy-2-alkylquinolines ofPseudomonas aeruginosa. Usingin silicoanalyses, we previously showed that thehmqABCDEFGoperon, which encodes enzymes involved in the biosynthesis of HMAQs, is carried by about one-third of Bcc strains, with considerable inter- and intra-species variability. In the present study, we investigated by PCR, using consensus primers, the distribution ofhmqABCDEFGin a collection of 313 Bcc strains (222 of clinical and 91 of environmental origins) - belonging to 18 Bcc species. We confirmed that the distribution is species-specific, although not all strains within a species carry thehmqABCDEFGoperon. Among the 30% of strains bearing thehmqABCDEFGoperon, we measured the total HMAQs production and showed that 90% of environmental isolates and 68% of clinically isolated Bcc produce detectable levels of HMAQs when cultured in TSB medium. For the strains having thehmqABCDEFGoperon but not producing HMAQs, we studied the transcription and showed that none expressed thehmqAgene under the specified culture conditions. Interestingly, thehmqABCDEFGoperon is more prevalent among plant root environment species (e.g.B. ambifaria, B. cepacia) and absent in species commonly found in chronically colonized individuals with cystic fibrosis (e.g.B. cenocepacia, B. multivorans), suggesting that the Hmq system could play a role in niche adaptation by influencing rhizosphere microbial community and could have been lost through evolution. Understanding the Hmq system and its regulation will provide clues concerning the production of HMAQs and their functions in Bcc.
First isolation and genetic characterization of Puumala orthohantavirus strains from France
Authors: Vulin Johann , Murri Séverine , Madrières Sarah , Galan Maxime , Tatard Caroline , Piry Sylvain , Vaccari Gabriele , D’agostino Claudia , Charbonnel Nathalie , Castel Guillaume , Marianneau Philippe 
Published: August 2020

AbstractPuumala orthohantavirus (PUUV) causes a mild form of haemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE), regularly diagnosed in Europe. France represents the western frontier of the expansion of NE in Europe with two distinct areas: an endemic area (north-eastern France) where PUUV circulates in rodent populations, with detection of many human NE cases, and a non-endemic area (south-western France) where the virus is not detected, with only a few human cases being reported. France is thus a relevant country in which to study the factors that influence the evolution of PUUV distribution. In this study, we describe for the first time the isolation of two PUUV strains from two distinct French geographical areas: Ardennes (endemic area) and Loiret (non-endemic area). To isolate PUUV efficiently, we selected wild bank voles (Myodes glareolus, the specific reservoir of PUUV) captured in these areas and that were seronegative for anti-PUUV IgG (ELISA), but showed a non-negligible viral RNA load in their lung tissue (qRT-PCR). With this study design, we were able to cultivate and maintain these two strains in Vero E6 cells and also propagate both strains in immunologically neutral bank voles efficiently and rapidly. Complete coding sequences of the S and M segments were determined by Sanger sequencing from RNA extracted from positive bank voles (naturally and experimentally infected) and from supernatants of Vero E6 cell extracts. For the M segment, nucleotide sequences were 100% identical for both strains. For the S segment, the amino-acid sequences from each strain revealed one mismatch between sequences obtained from tissue and from cell supernatants, revealing distinct “bank vole” and a “cell” molecular profile. High-throughput sequencing confirmed Sanger results, and provided a better assessment of the impact of isolation methods on intra-host viral diversity.
Evading resistance to gene drives
Authors: Gomulkiewicz Richard , Thies Micki L. , Bull James J. 
Published: August 2020

ABSTRACTGene drives offer the possibility of altering and even suppressing wild populations of countless plant and animal species, and CRISPR technology now provides the technical feasibility of engineering them. However, population-suppression gene drives are prone to select resistance, should it arise. Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially. Previous models assumed resistance is allelic to the drive. We relax this assumption and show that linkage between the resistance and drive loci is critical to the evolution of resistance and that evolution of resistance requires (negative) linkage disequilibrium between the two loci. When the two loci are unlinked or only partially so, a suppression drive that causes limited inviability can evolve to fixation while causing only a minor increase in resistance frequency. Once fixed, the drive allele no longer selects resistance. Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion
Authors: Flower Thomas G. , Buffalo Cosmo Z. , Hooy Richard M. , Allaire Marc , Ren Xuefeng , Hurley James H. 
Published: August 2020

AbstractThe molecular basis for the severity and rapid spread of the COVID-19 disease caused by SARS-CoV-2 is largely unknown. ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SARS-CoV-2 ORF8 was determined at 2.04 Å resolution by x-ray crystallography. The structure reveals a ~60 residue core similar to SARS-CoV ORF7a with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. A covalent disulfide-linked dimer is formed through an N-terminal sequence specific to SARS-CoV-2, while a separate non-covalent interface is formed by another SARS-CoV-2-specific sequence,73YIDI76. Together the presence of these interfaces shows how SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.
Divergent influenza-like viruses of amphibians and fish support an ancient evolutionary association
Authors: Parry Rhys , Wille Michelle , Turnbull Olivia M. H. , Geoghegan Jemma L. , Holmes Edward C. 
Published: August 2020

AbstractInfluenza viruses (family Orthomyxoviridae) infect a variety of vertebrates, including birds, humans, and other mammals. Recent metatranscriptomic studies have uncovered divergent influenza viruses in amphibians, fish and jawless vertebrates, suggesting that these viruses may be widely distributed. We sought to identify additional vertebrate influenza-like viruses through the analysis of publicly available RNA sequencing data. Accordingly, by data mining, we identified the complete coding segments of five divergent vertebrate influenza-like viruses. Three fell as sister lineages to influenza B virus: salamander influenza-like virus in Mexican walking fish (Ambystoma mexicanum) and plateau tiger salamander (Ambystoma velasci), siamese algae-eater influenza-like virus in siamese algae-eater fish (Gyrinocheilus aymonieri) and chum salmon influenza-like virus in chum salmon (Oncorhynchus keta). Similarly, we identified two influenza-like viruses of amphibians that fell as sister lineages to influenza D virus: cane toad influenza-like virus and the ornate chorus frog influenza-like virus, in the cane toad (Rhinella marina) and ornate chorus frog (Microhyla fissipes), respectively. Despite their divergent phylogenetic positions, these viruses retained segment conservation and splicing consistent with transcriptional regulation in influenza B and influenza D viruses, and were detected in respiratory tissues. These data suggest that influenza viruses have been associated with vertebrates for their entire evolutionary history.
Cellular and behavioral characterization ofPcdh19mutant mice: subtle molecular changes, increased exploratory behavior and an impact of social environment
Authors: Galindo-Riera Natalia , Newbold Sylvia Adriana , Sledziowska Monika , Griffiths Jessica , Mire Erik , Martinez-Garay Isabel 
Published: August 2020

ABSTRACTMutations in the X-linked cell adhesion protein PCDH19 lead to seizures, cognitive impairment and other behavioral comorbidities when present in a mosaic pattern. Neither the molecular mechanisms underpinning this disorder, nor the function of PCDH19 itself are well understood. By combining RNAin situhybridization with immunohistochemistry and analyzing single cell RNAseq datasets, we provide a first account of the subtypes of neurons expressingPcdh19/PCDH19, both in the mouse and the human cortex. Our quantitative analysis of thePcdh19mutant mouse reveals subtle changes in cortical layer composition, with no major alterations of the main axonal tracts. However,Pcdh19mutant animals, particularly females, display preweaning behavioral changes, including reduced anxiety and increased exploratory behavior. Our experiments also reveal an effect of the social environment on the behavior of wild-type littermates ofPcdh19mutant mice when compared with wild-type animals not housed with mutants. This is a second case of a mutated X-linked gene encoding a membrane protein expressed in the developing cortex impacting the behavior of co-housed wild-type littermates.
Aligning firm's value system and open innovation: a new framework of business process management beyond the business model innovation
Authors: Abdulkader Bisan , Magni Domitilla , Cillo Valentina , Papa Armando , Micera Roberto 
Published: August 2020

PurposeBusiness process management (BPM) supports the creation and capture of firm value. In a dynamic context, the current approach to BPM appears to be limited and static in the face of the challenges posed by the firm's open innovation (OI) ecosystem. The main purpose of this paper is to shed light on the value co-creation through the integration of OI principles and mechanisms of value system.Design/methodology/approachTo this aim, the paper suggested a conceptual integration of strategy and operations literature on OI and the firm's value creation system. This analysis adopted BPM lenses with specific attention to the alignment between value creation and value capture. Applying BPM lenses to the process of creating shared value sought the attainment of a comprehensive system of decisions articulated between strategy and operations.FindingsThe paper pinpoints key links between strategy models and operational planning, thus proposing a new framework that integrates the characteristics of value system and OI. The paper elaborates a new theoretical framework rooted in the extant literature conducted in BPM, business strategy and business model innovation (BMI) fields.Originality/valueThis paper aims to fill the gap in the literature in which strategy models are separately treated from the operational ones. This conceptual effort contributes to the extant literature by drawing upon a comprehensive frameworkand mapping the complex set of interactions between the firm's value chain and its innovation ecosystem.
One finance: dealing with Nigeria’s highly-skilled talent constraints
Authors: Magau Mpho Dennis , Maritz Jaco 
Published: August 2020

Learning outcomes
This case study aims to provide students with: an understanding of the unique challenges companies in Africa face in attracting and retaining highly-skilled human resources. The ability to critically evaluate various talent recruitment, development and retention options available to companies in Africa.

Case overview/synopsis
This case study examines the talent management challenges faced by Chijioke Dozie, CEO of Nigeria-based financial services company One Finance (OneFi). Under the brand name Carbon, OneFi operated a digital financial services app that offered loans, bill payments, an investment platform and an electronic wallet. However, Nigeria did not have many professionals with experience in consumer lending and certain technical skills, particularly data scientists and software engineers, was hard to find. Data scientists, for instance, were not only in short supply in Nigeria but also they were in high demand globally. OneFi, therefore, competed against top employers throughout the world, but with a start-up budget. OneFi’s talent management dilemma is a common challenge faced by companies operating within under-developed African economies. The insights and learnings from this case are, therefore, also applicable to other businesses on the continent.

Complexity academic level
MBA Post Grad.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 1: Accounting and Finance.
Connecting the past with the present: the development of research on pedagogy in entrepreneurial education
Authors: Gabrielsson Jonas , Hägg Gustav , Landström Hans , Politis Diamanto 
Published: August 2020

PurposeThe purpose of the paper is to explore knowledge accumulation in research on pedagogy in entrepreneurship education, with particular attention to how core journal outlets, core topics and core scholarly works have developed over time.Design/methodology/approachThe authors combine a systematic literature review technique and bibliometric analysis to depict the development of this stream of research in the period 1995–2018.FindingsFindings from the analyses suggests that research addressing pedagogy in entrepreneurship education has developed into a coherent research theme over the past decade, with a noticeable cognitive structure in core research topics and core works, as well as a number of core journal outlets for debates and dissemination of findings.Research limitations/implicationsThe study is anchored in a bibliometric research tradition and influenced by the strengths and weaknesses of this approach.Originality/valueThe paper provided contributes to the understanding of knowledge accumulation in research addressing pedagogy in entrepreneurial education.
Assessment of food heritage to improve virtuous cycles
Authors: Khatami Fahimeh , Sorano Enrico , Bechis Marco 
Published: August 2020

PurposeThe purpose of this paper is to contribute the advancement of knowledge on food heritage and indigenous entrepreneurship in a non-Western country, specifically in the Persian gardens as the touristic destination for increasing the tourism and food businesses in Iran.Design/methodology/approachThe methodological approach adopted is based on qualitative and quantitative approaches to compare two representative gardens named as Bagh-Chehel-Sotoun and Bagh-Fin, as famous examples of a Persian garden in Iran. The methods supported the research to explain the lack of strategies for improving virtuous cycles in Persian gardens despite their potentials as the main places to attract many tourists.FindingsRegarding local food and the quality of servicing, most of the visitors and tourists (85–90%) had interest to test local and traditional foods around both gardens, but they had no sufficient awareness of Iranian traditional foods. According to the tourists’ interests, the authors concluded the lack of servicing and facilities to present and introduce local and traditional food for tourists.Research limitations/implicationsDespite the limitation of local food services and lack of awareness of tourists about local foods, the implication of the study offers possible avenues to promote local food business.Practical implicationsThe results could be useful for cultural heritage and tourism organizations and for investors in the economic sector due to more exploitation of the tourism industry.Originality/valueThe paper is the first work evaluating the Persian garden with a new perspective of local foods in Iran.
The effects of tourist experiential quality on perceived value and satisfaction with bed and breakfast stays in southwestern China
Authors: Feng Yan , Chen Xiaolian , Lai Ivan 
Published: August 2020

PurposeB&B stays have enjoyed popularity in China over recent decades. This study examines the impacts of the three dimensions of tourist experiential quality on the perceived functional and emotional value and customer satisfaction with B&B stays in Southwestern China.Design/methodology/approachQuestionnaires were collected from 433 Chinese visitors in Southwestern China. Partial least squares–structural equation modeling (PLS-SEM) was used to test the significance of the relationship that exists among experiential quality, perceived value and tourist satisfaction.FindingsThe research results proved that experiential quality predicts customer satisfaction with B&B stays as mediated by perceived functional and emotional values. The specific experiential quality - fun – has the strongest effect on both perceived functional value and emotional value between the three dimensions of experiential quality.Research limitations/implicationsSince fun is viewed as the most significant element, B&B providers should consider creating a more joyful encounter for tourists. They should enrich the activities and improve service to strengthen the experiential quality perceived by the tourists. Both relational experiences and authentic local experiences should be incorporated into the activities and services provided.Originality/valueThis is likely to be the first study to investigate the influence of three dimensions of experiential quality on perceived functional and emotional value and satisfaction from the B&B industry in China. The findings provide value through actionable insights into experiential qualities, functional and emotional values that drive tourist satisfaction.