bluuebunny/crossref_metadata_2025_split huggingface dataset:
High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani
Authors: Negreira Gabriel H. , Monsieurs Pieter , Imamura Hideo , Maes Ilse , Kuk Nada , Yagoubat Akila , Van den Broeck Frederik , Sterkers Yvon , Dujardin Jean-Claude , Domagalska Malgorzata A. 
Published: May 2021

AbstractLeishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two Leishmania clonal populations representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations. MA usually affected a defined subset of chromosomes, of which some display an enrichment in snoRNA genes which could represent an adaptative benefit to the amplification of these chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.Note to the BioRxiv communityThe present preprint is a revision of an older preprint posted on 06th March 2020 on BioRxiv (https://www.biorxiv.org/content/10.1101/2020.03.05.976233v1). Here we included two extra samples in our single-cell genome sequencing (SCGS) analysis – the BPK081 cl8 clone (a nearly euploid strain) and a population consisting of a mixture of four L. donovani strains which was used as control for high levels of mosaicism in aneuploidy and for estimation of doublets. We also upgraded the bioinformatics pipeline to determine single-cell karyotypes and performed new fluorescence in situ hybridization (FISH) analysis. The new findings observed especially in the BPK081 cl8 led to a reformulation of the text, a new hypothesis for the evolution of mosaicism and a general restructuring of the article. Therefore, the older preprint is obsolete.
Cannabinoid tetrad effects of oral Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in male and female rats: sex, dose-effects and time course evaluations
Authors: Moore Catherine F. , Weerts Elise M. 
Published: May 2021

AbstractRationale The legalization of medicinal use of Cannabis sativa in most US states and the removal of hemp from the Drug Enforcement Agency (DEA) controlled substances act has resulted in a proliferation of products containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for oral consumption (e.g., edibles, oils and tinctures) that are being used for recreational and medicinal purposes. Objective This study examined the effects of cannabinoids THC and CBD when administered orally on measures of pain sensitivity, body temperature, locomotor activity, and catalepsy (i.e., cannabinoid tetrad) in male and female Sprague Dawley rats. Methods Rats (N=24, 6 per sex/drug group) were administered THC (1-20 mg/kg), CBD (3-30 mg/kg), or sesame oil via oral gavage. Thermal and mechanical pain sensitivity (tail flick assay, von Frey test), rectal measurements for body temperature, locomotor activity, and the bar-test of catalepsy were completed. A separate group of rats (N=8/4 per sex) were administered morphine (5-20 mg/kg; intraperitoneal, IP) and evaluated for pain sensitivity as a positive control. Results We observed classic tetrad effects of antinociception, hypothermia, hyper- and hypolocomotion, and catalepsy after oral administration of THC that were long lasting (>7 hours). CBD modestly increased mechanical pain sensitivity and produced sex-dependent effects on body temperature and locomotor activity. Conclusions Oral THC and CBD produced long lasting effects, that differed in magnitude and time course when compared with other routes of administration. Examination of cannabinoid effects administered via different routes of administration, species, and in both males and females is critical to enhance translation.
Neuron specific ablation of eIF5A or deoxyhypusine synthase leads to impairment in development and cognitive functions in mice
Authors: Kar Rajesh Kumar , Hanner Ashleigh S. , Starost Matthew F. , Springer Danielle , Mastracci Teresa L. , Mirmira Raghavendra G. , Park Myung Hee 
Published: May 2021

AbstractEukaryotic initiation factor 5A (eIF5A) is an essential factor with a unique amino acid, hypusine, required for its activity. Hypusine is formed exclusively in eIF5A by a post-translational modification involving two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Each of the three genes, Eif5a, Dhps or Dohh is required for mouse embryonic development. Variants in EIF5A or DHPS were recently identified as the genetic basis underlying certain rare neurodevelopmental disorders in humans. To investigate the roles of eIF5A and DHPS in brain development, we have generated four conditional knockout mouse strains using the Emx1-Cre or Camk2a-Cre strain and examined the effects of temporal- and region-specific deletion of Eif5a or Dhps. The conditional deletion of Dhps or Eif5a by Emx1 promotor driven Cre expression (E.9.5, cortex and hippocampus) led to gross defects in forebrain development, reduced growth and premature death. On the other hand, the conditional deletion of Dhps or Eif5a by Camk2a-promoter driven Cre expression (postnatal, mainly in the CA1 region of hippocampus) did not lead to global developmental defects; rather, these knockout animals exhibited severe impairment in spatial learning, contextual learning and memory, when subjected to the Morris Water Maze test and a contextual learning test. In both models, the Dhps knockout mice displayed more severe impairment than their Eif5a knockout counterparts. The observed defects in brain, global development or cognitive functions most likely result from translation errors due to a deficiency in active, hypusinated eIF5A. Our study underscores the important roles of eIF5A and DHPS in neurodevelopment.SignificanceeIF5A, an essential translation factor, is the only protein that undergoes a unique posttranslational modification, that converts lysine to hypusine by conjugation of the aminobutyl moiety from the polyamine spermidine. Hypusine biosynthesis occurs by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Mutations in EIF5A or DHPS have been associated with rare neurodevelopmental disorders in humans. To understand the mechanisms underlying the pathogenesis of the disease, we generated mutant mice with brain-specific deletions of Eif5a or Dhps. The Eif5a and Dhps conditional knockout mice exhibited impairment in brain development, growth and cognitive functions. These animal models may serve as useful tools in the development of therapies against the eIF5A- or DHPS-associated neurodevelopmental disorders.
Delayed DNA replication in haploid human embryonic stem cells
Authors: Edwards Matthew M. , Zuccaro Michael V. , Sagi Ido , Ding Qiliang , Vershkov Dan , Benvenisty Nissim , Egli Dieter , Koren Amnon 
Published: May 2021

AbstractHaploid human embryonic stem cells (ESCs) provide a powerful genetic system but diploidize at high rates. We hypothesized that diploidization results from aberrant DNA replication. To test this, we profiled DNA replication timing in isogenic haploid and diploid ESCs. The greatest difference was the earlier replication of the X chromosome in haploids, consistent with the lack of X chromosome inactivation. Surprisingly, we also identified 21 autosomal regions that had dramatically delayed replication in haploids, extending beyond the normal S phase and into G2/M. Haploid-delays comprised a unique set of quiescent genomic regions that are also under-replicated in polyploid placental cells. The same delays were observed in female ESCs with two active X chromosomes, suggesting that increased X chromosome dosage may cause delayed autosomal replication. We propose that incomplete replication at the onset of mitosis could prevent cell division and result in re-entry into the cell cycle and whole genome duplication.HighlightsDNA replication timing of haploid ESCs profiled by WGSExtreme replication timing delays in haploid ESCs at unique genomic regionsReplication delays associate with X-chromosome dosage in multiple systemsReplication delayed regions correspond to underreplication in mouse polyploid cells
Plans to vaccinate children for COVID-19: a survey of US parents
Authors: Teasdale Chloe A. , Borrell Luisa N. , Kimball Spencer , Rinke Michael L. , Rane Madhura , Fleary Sasha A. , Nash Denis 
Published: May 2021

ABSTRACTIn a national online survey of 2,074 US parents conducted in March 2021, 49.4% reported plans to vaccinate their child for COVID-19 when available. Lower income and less education were associated with greater parental vaccine hesitancy/resistance, while safety, effectiveness and lack of need were the primary reasons for vaccine hesitancy/resistance.
NMNAT promotes glioma growth through regulating post-translational modifications of p53 to inhibit apoptosis
Authors: Liu Jiaqi , Tao Xianzun , Zhu Yi , Li Chong , Ruan Kai , Diaz-Perez Zoraida , Wang Hongbo , Zhai R. Grace 
Published: May 2021

ABSTRACTGliomas are highly malignant brain tumors with poor prognosis and short survival. NAD+ has been shown to impact multiple processes that are dysregulated in cancer; however, anti-cancer therapies targeting NAD+ synthesis have been unsuccessful due to insufficient mechanistic understanding. Here we adapted a Drosophila glial neoplasia model and discovered the genetic requirement for NAD+ synthase nicotinamide mononucleotide adenylyltransferase (NMNAT) in glioma progression in vivo and in human glioma cells. Overexpressing enzymatically active NMNAT significantly promotes glial neoplasia growth and reduces animal viability. Mechanistic analysis suggests that NMNAT interferes with DNA damage-p53-caspase-3 apoptosis signaling pathway by enhancing NAD+-dependent posttranslational modifications (PTMs) poly(ADP-ribosyl)ation (PARylation) and deacetylation of p53. Interestingly, NMNAT forms a complex with p53 and PTM enzyme PARP1 to facilitate PARylation. As PARylation and deacetylation reduce p53 pro-apoptotic activity, our results demonstrate that NMNAT promotes glioma progression through regulating p53 post-translational modifications. Our findings reveal a novel tumorigenic mechanism involving protein complex formation of p53 with NAD+ synthetic enzyme NMNAT and NAD+-dependent PTM enzymes that regulates glioma growth.
Evaluation of Machine Learning predictions of a highly resolved time series of Chlorophyll-a concentration
Authors: de L. L. de Amorim Felipe , Rick Johannes , Lohmann Gerrit , Wiltshire Karen Helen 
Published: May 2021

AbstractPelagic Chlorophyll-a concentrations are key for evaluation of the environmental status and productivity of marine systems. In this study, chlorophyll-a concentrations for the Helgoland Roads Time Series were modeled using a number of measured water and environmental parameters. We chose three common Machine Learning algorithms from the literature: Support Vector Machine Regressor, Neural Networks Multi-layer Perceptron Regressor and Random Forest Regressor. Results showed that Support Vector Machine Regressor slightly outperformed other models. The evaluation with a test dataset and verification with an independent validation dataset for chlorophyll-a concentrations showed a good generalization capacity, evaluated by the root mean squared errors of less than 1 μg L−1. Feature selection and engineering are important and improved the models significantly, as measured in performance, improving by a minimum of 48% the adjusted R2. We tested SARIMA in comparison and found that the univariate nature of SARIMA does not allow for better results than the Machine Learning models. Additionally, the computer processing time needed was much higher (prohibitive) for SARIMA.
Phase transition in an organic ferroelectric: glycinium phosphite, with and without X-ray radiation damage
Authors: Bogdanov Nikita E. , Zakharov Boris A. , Chernyshov Dmitry , Pattison Philip , Boldyreva Elena V. 
Published: May 2021

Thermal evolution of an organic ferroelectric, namely, glycinium phosphite, was probed by multi-temperature single-crystal diffraction using synchrotron radiation and also by a similar experiment with a laboratory X-ray diffractometer. Both series of measurements showed a transition from the paraelectric to the ferroelectric state at nearly the same temperature,Tc = 225 K. Temperature evolution of the unit-cell parameters and volume are drastically different for the synchrotron and laboratory data. The latter case corresponds to previous reports and shows an expected contraction of the cell on cooling. The data collected with the synchrotron beam show an abnormal nonlinear increase in volume on cooling. Structure analysis shows that this volume increase is accompanied by a suppression of scattering at high angles and an apparent increase of the anisotropic displacement parameters for all atoms; we therefore link these effects to radiation damage accumulated during consecutive data collections. The effects of radiation on the formation of the polar structure of ferroelectric glycinium phosphite is discussed together with the advantages and drawbacks of synchrotron experimentation with fine temperature sampling.
Heritagisation of pop culture by museums and an analysis of visitor feedback
Authors: Waller David S. , Waller Helen J. 
Published: May 2021

PurposeIn recent years, there has been a “heritagisation” of pop culture, including music, whereby cultural institutions, such as galleries and museums in primarily Western countries, have run exhibitions based on pop culture to successfully market to a new audience of visitors. The purpose of this qualitative study is to explore the issue of the “heritagisation” of pop culture by museums and observe visitor response to a specific music-related exhibition, linking intangible and tangible elements of the exhibition to provide a framework to understand the visitor experience.Design/methodology/approachThe purpose will be achieved by observing the “heritagisation” of pop culture in the literature and past exhibitions, proposing how cultural institutions have linked the intangible and tangible elements of music in pop culture for an exhibition and observe visitors' feedback from online comments posted on Tripadvisor undertaken during the original “David Bowie is” exhibition at the Victoria and Albert Museum (V&A), London.FindingsFrom the Leximancer analysis, a new conceptual framework for visitor experience at an exhibition was developed, which contains three visitor-related categories: pre-exhibition, exhibition space and exhibition experience, with five themes (tickets, exhibition, displayed objects, David Bowie and visitors) and 41 text concepts.Practical implicationsFor cultural institutions the implications are that there can be opportunities to curate exhibitions on pop culture or music-related themes, which can include intangible and tangible elements, such as songs, videos, tickets, costumes, musical instruments and posters. These exhibitions can also explore the changing socio/political/historical/cultural background that contextualises pop cultural history.Originality/valueThis theory-building study advances the body of knowledge as it links music in pop culture and cultural institutions, specifically in this case a highly successful music-related exhibition at a museum, and provides a theoretical model based on tangibility elements. Further, it analyses museum visitor comments by using the qualitative software program, Leximancer, to develop a new conceptual framework for visitor experience.
Extent of stakeholder management practices in building projects procured by private corporate organisations in Nigeria
Authors: Olatunde Nathaniel Ayinde , Odeyinka Henry A. 
Published: May 2021

PurposeStudies on stakeholder management (SM) in developing countries have largely focused on public projects. However, projects of private organisations also need much improvement. The purpose of the study was to examine the extent of SM practices in building projects procured by private corporate organisations.Design/methodology/approachPurposive sampling technique was used to select project managers (PMs) and client representatives (CRs) who have been involved in projects procured by private corporate organisations between 2008 and 2017 in Southwestern Nigeria. The PMs are comprised of executive and non-executive PMs as well as contract administrators. Both the PMs and CRs were requested to provide information on one building project in which they were involved within the period under consideration. The data collected were analysed using mean score (MS) analysis, t-test, and analysis of variance.FindingsThe results showed that structured SM processes were followed in only 30.65% of building projects procured by private corporate organisations in the study area. Results further showed on a five-point scale 5-max scale that SM practice was highest with an MS of 3.92 on projects where executive PMs were appointed and lowest (MS = 2.85) on projects where PMs were appointed as contract administrators. Furthermore, it was found that respondents placed the highest premium (MS = 3.73) on stakeholder identification while they placed the lowest premium (MS = 3.45) on developing implementation strategies and stakeholder classification.Practical implicationsThe study examines the status quo regarding SM practice in the study area in order to devise a means of refinement.Originality/valueThe study is an attempt to evaluate the premium placed on different components of SM practices by differing categories of project managers.
Measuring a multidimensional green brand equity: a tool for entrepreneurship development
Authors: Cuesta-Valiño Pedro , Gutiérrez-Rodríguez Pablo , Sierra-Fernández María-Pilar , Aguirre García María-Belén 
Published: May 2021

PurposeThis study analyses the dimensions of the brand equity of organic agri-food products using a multidimensional approach. It also examines the direct and indirect relationships of this brand equity with consumers’ green satisfaction and the green image of organic agri-food products. The green brand can be understood as a tool for entrepreneurial development.Design/methodology/approachThe researchers develop a conceptual framework highlighting the dimensions of the green brand equity focusing on five constructs (green brand loyalty, green perceived quality, green brand associations, green brand awareness and the new dimension of green brand emotion), green satisfaction and green brand image. The sample consisted of 392 people aged over 18 who were occasional or habitual consumers of organic agri-food products. Partial least squares (PLS), a structural equation modelling (SEM) tool, was used in the analyses.FindingsThe results of this study show that the different dimensions of green brand equity (except for green brand awareness) reflect this variable and are important factors in its perception by consumers. This study differs from others in that it treats green brand equity as a truly multidimensional variable made up of different dimensions with different measurement scales. The study also demonstrates the importance of green satisfaction and green brand image as antecedents of green brand equity.Practical implicationsThe measurement scale for green brand equity developed in this study provides entrepreneurs of organic agri-foods with a method for evaluating consumer perception of green brand equity based on those dimensions that are truly significant.Originality/valueThis is the first study to explore the relationships of green brand equity—as a multidimensional concept—with other variables, such as green satisfaction and green image.
Satisfaction and value-in-use perceived by university students from the influence of the built environment, price fairness and teaching care
Authors: Benetti Corrêa da Silva Marcelo , Matte Juliana , Bebber Suélen , Libardi Bianca , Fachinelli Ana Cristina 
Published: May 2021

PurposeThis research goal was to analyze factors that may influence value-in-use and satisfaction perceived by university students, from the built environment, price fairness and teaching care.Design/methodology/approachFor this purpose, a survey was conducted with 900 students from a university in southern Brazil.FindingsThe main results proved that the antecedents considered in the study have a significant and positive influence on the value-in-use and satisfaction of university students. Furthermore, the built environment, price fairness, teaching care and satisfaction explained 87.8% of the value-in-use of students, while the built environment, price fairness and teaching care explained 74.9% of student satisfaction.Originality/valueThe study proved that after receiving the educational service, if the student can apply his or her acquired knowledge and skills, he or she will find a fair price, will be satisfied and will obtain value in the service purchased. Thus, even if the educational market is changing in recent years, the importance of the teacher and the built environment are factors that influence price fairness and increase the satisfaction and value-in-use perceived by the student.