bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics
Authors: Buchholz David E. , Carroll Thomas S. , Kocabas Arif , Zhu Xiaodong , Behesti Hourinaz , Faust Phyllis L. , Stalbow Lauren , Fang Yin , Hatten Mary E. 
Published: January 2020

AbstractComparative transcriptomics between differentiating human pluripotent stem cells (hPSC) and developing mouse neurons offers a powerful approach to compare genetic and epigenetic pathways in human and mouse neurons. To analyze human Purkinje cell (PC) differentiation, we optimized a protocol to generate hPSC-PCs that formed synapses when cultured with mouse cerebellar glia and granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. To directly compare global gene expression of hPSC-PCs with developing mouse PCs, we used translating ribosomal affinity purification (TRAP). As a first step, we usedTg(Pcp2-L10a-Egfp)TRAP mice to profile actively transcribed genes in developing postnatal mouse PCs, and used metagene projection to identify the most salient patterns of PC gene expression over time. We then created a transgenicPcp2-L10a-EgfpTRAP hESC line to profile gene expression in differentiating hPSC-PCs, finding that the key gene expression pathways of differentiated hPSC-PCs most closely matched those of late juvenile, mouse PCs (P21). Comparative bioinformatics identified classical PC gene signatures as well as novel mitochondrial and autophagy gene pathways during the differentiation of both mouse and human PCs. In addition, we identified genes expressed in hPSC-PCs but not mouse PCs and confirmed protein expression of a novel human PC gene, CD40LG, expressed in both hPSC-PCs and native human cerebellar tissue. This study therefore provides the first direct comparison of hPSC-PC and mouse PC gene expression and a robust method for generating differentiated hPSC-PCs with human-specific gene expression for modeling developmental and degenerative cerebellar disorders.Significance StatementTo compare global gene expression features of differentiating human pluripotent stem cell-derived Purkinje cells (hPSC-PC) and developing mouse Purkinje cells (PC) we derived hPSC-PCs and compared gene expression datasets from human and mouse PCs. We optimized a differentiation protocol that generated hPSC-PCs most similar in gene expression to mouse P21 PCs. Metagene projection analysis of mouse PC gene expression over postnatal development identified both classical PC marker genes as well as novel mitochondrial and autophagy gene pathways. These key gene expression patterns were conserved in differentiating hPSC-PCs. We further identified differences in timing and expression of key gene sets between mouse and hPSC-PCs and confirmed expression of a novel human PC marker, CD40LG, in human cerebellar tissue.
Infestation dynamics between parasitic Antarctic fish leeches (Piscicolidae) and their crocodile icefish hosts (Channichthyidae)
Authors: Parker Elyse , Jones Christopher , Arana Patricio M. , Alegría Nicolás A. , Sarralde Roberto , Gallardo Francisco , Phillips A.J. , Williams B.W. , Dornburg A. 
Published: January 2020

AbstractAn understanding of host-parasite interactions represents an important, but often overlooked, axis for predicting how marine biodiversity may be impacted by continued environmental change over the next century. For host and parasite communities in the Southern Ocean, investigations of many major groups of parasites have largely been limited to taxonomic and phylogenetic studies, creating an urgent need for the collection of baseline ecological data if we are to detect changes in host-parasite interactions in the future. Here, we survey three species of Crocodile icefish (Notothenioidei: Channichthyidae) collected from two island archipelagos in Antarctica’s South Scotia Arc region for evidence of leech infestations. Specifically, we report on infestation prevalence and intensity of three leech species (Trulliobdella bacilliformis,Trulliobdella capitis, andNototheniobdella sawyeri) on the host fish speciesChaenocephalus aceratus,Champsocephalus gunnari, andChionodraco rastrospinosus.Additionally, we characterize spatial patterns of relative abundances of each leech species across the Elephant and South Orkney Islands, size distribution of parasitized fish, and patterns of host and attachment site specificity. Our results reveal high levels of attachment area fidelity for each leech species. These results suggest skin thickness and density of the vascular network constrain leech attachment sites and further suggest trophic transmission to be an important axis of parasitization. We also demonstrate that, while leech species appear to be clustered spatially, this clustering does not appear to be correlated with fish biomass. This study illuminates the complex interactions among fish hosts and leech parasites in the Southern Ocean and lays the groundwork for future studies of Antarctic marine leech ecology that can aid in forecasting how host-parasite interactions may shift in the face of ongoing climate change.
Multiple resource use strategies confer resilience to the socio-ecosystem in a protected area in the Yucatan Peninsula, Mexico
Authors: García Jácome Luis Guillermo , García-Frapolli Eduardo , Moheno Martha Bonilla , Rivera Coral Rangel , Benítez Mariana , Ramos-Fernández Gabriel 
Published: January 2020

ABSTRACTNatural Protected Areas (NPAs) are the main biodiversity conservation strategy in Mexico. Generally, NPAs are established on the territories of indigenous and rural groups driving important changes in their local resource management practices. In this paper we study the case ofOtoch Ma’ax Yetel Kooh, an NPA in the Yucatan Peninsula, Mexico, that has been studied in a multidisciplinary way for more than twenty years. This reserve and its buffer zone is homeland to Yucatec Mayan communities that until recently used to manage their resources following a multiple use strategy (MUS), which involves local agricultural practices and has been proposed as resilience-enhancing mechanism. However, due to the restrictions imposed by the decree of the reserve and the growth of tourism in the region, some of these communities have started to abandon the MUS and specialize on tourism-related activities. We build a dynamical computational model to explore the effects of some of these changes on the capacity of this NPA to conserve the biodiversity and on the resilience of households to some frequent disturbances in the region. The model, through the incorporation of agent-based and boolean network modelling, explores the interaction between the forest, the monkey population and some productive activities done by the households (milpa agriculture, ecotourism, agriculture, charcoal production). We calibrated the model, explored its sensibility, compared it with empirical data and simulated different management scenarios. Our results suggest that those management strategies that do not exclude traditional activities may be compatible with conservation objectives, supporting previous studies. Also, our results support the hypothesis that the MUS, throughout a balanced integration of traditional and alternative activities, is a mechanism to enhance household resilience in terms of income and food availability, as it reduces variability and increases the resistance to some disturbances. Our study, in addition to highlighting the importance of local management practices for resilience, also illustrates how computational modeling and systems perspective are effective means of integrating and synthesizing information from different sources.
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation
Authors: Passmore Josiah B. , Carmichael Ruth E. , Schrader Tina A. , Godinho Luis F. , Ferdinandusse Sacha , Lismont Celien , Wang Yunhong , Hacker Christian , Islinger Markus , Fransen Marc , Richards David M. , Freisinger Peter , Schrader Michael 
Published: January 2020

AbstractPeroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed.
Partitioning gene-based variance of complex traits by gene score regression
Authors: Zhang Wenmin , Li Si Yi , Liu Tianyi , Li Yue 
Published: January 2020

AbstractThe majority of genome-wide association studies (GWAS) loci are not annotated to known genes in the human genome, which renders biological interpretations difficult. Transcriptome-wide association studies (TWAS) associate complex traits with genotype-based prediction of gene expression deriving from expression quantitative loci(eQTL) studies, thus improving the interpretability of GWAS findings. However, these results can sometimes suffer from a high false positive rate, because predicted expression of different genes may be highly correlated due to linkage disequilibrium between eQTL. We propose a novel statistical method, Gene Score Regression (GSR), to detect causal gene sets for complex traits while accounting for gene-to-gene correlations. We consider non-causal genes that are highly correlated with the causal genes will also exhibit a high marginal association with the complex trait. Consequently, by regressing on the marginal associations of complex traits with the sum of the gene-to-gene correlations in each gene set, we can assess the amount of variance of the complex traits explained by the predicted expression of the genes in each gene set and identify plausible causal gene sets. GSR can operate either on GWAS summary statistics or observed gene expression. Therefore, it may be widely applied to annotate GWAS results and identify the underlying biological pathways. We demonstrate the high accuracy and computational efficiency of GSR compared to state-of-the-art methods through simulations and real data applications. GSR is openly available athttps://github.com/li-lab-mcgill/GSR.
GAPDH controls extracellular vesicle biogenesis and enhances therapeutic potential of EVs in silencing the Huntingtin gene in mice via siRNA delivery
Authors: Dar Ghulam Hassan , Mendes Cláudia C. , Kuan Wei-Li , Conceição Mariana , El-Andaloussi Samir , Mager Imre , Roberts Thomas C. , Barker Roger A. , Goberdhan Deborah C. I. , Wilson Clive , Wood Matthew J.A. 
Published: January 2020

AbstractExtracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication and pathophysiology. Their capacity to transfer biomolecules between cells has sparked efforts to bioengineer EVs as drug delivery vehicles. However, a better understanding of EV biogenesis mechanisms and function is required to unleash their considerable therapeutic potential. Here we demonstrate a novel role for GAPDH, a glycolytic enzyme, in EV assembly and secretion, and we exploit these findings to develop a GAPDH-based methodology to load therapeutic siRNAs onto EVs for targeted drug delivery to the brain. In a series of experiments, we observe high levels of GAPDH binding to the outer surface of EVsviaa phosphatidylserine binding motif, designated as G58, and discover that the tetrameric nature of GAPDH promotes extensive EV aggregation. Studies in aDrosophilaEV biogenesis model demonstrate that GAPDH is absolutely required for normal generation of intraluminal vesicles in endosomal compartments and promotes vesicle clustering both inside and outside the cell. Fusing a GAPDH-derived G58 peptide to dsRNA-binding motifs permits highly efficient loading of RNA-based drugs such as siRNA onto the surface of EVs. Such vesicles efficiently deliver siRNA to target cellsin vitroand into the brain of a Huntington’s disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in multiple anatomical regions of the brain and modulation of phenotypic features of disease. Taken together, our study demonstrates a novel role for GAPDH in EV biogenesis, and that the presence of free GAPDH binding sites on EVs can be effectively exploited to substantially enhance the therapeutic potential of EV-mediated drug delivery to the brain.
Improved, two-stage protein expression and purification via autoinduction of both autolysis and auto DNA/RNA hydrolysis conferred by phage lysozyme and DNA/RNA endonuclease
Authors: Menacho-Melgar Romel , Moreb Eirik A. , Efromson John P. , Lynch Michael D. 
Published: January 2020

AbstractWe report improved release of recombinant proteins inE. coli, which relies on combined cellular autolysis and DNA/RNA autohydrolysis, conferred by the tightly controlled autoinduction of both phage lysozyme and the non specific DNA/RNA endonuclease fromS. marcescens. Autoinduction occurs in a two-stage process wherein heterologous protein expression and autolysis enzymes are induced upon entry into stationary phase by phosphate depletion. Cytoplasmic lysozyme and periplasmic endonuclease are kept from inducing lysis until membrane integrity is disrupted. Post cell harvest, the addition of detergent (0.1% Triton-X100) and a single 30 minutes freezer thaw cycle results in > 90% release of protein (GFP). This cellular lysis is accompanied by complete oligonucleotide hydrolysis. The approach has been validated for shake flask cultures, high throughput cultivation in microtiter plates and larger scale stirred-tank bioreactors. This tightly controlled system enables robust growth and resistance to lysis in routine media when cells are propagated and autolysis/hydrolysis genes are only induced upon phosphate depletion.HighlightsAutoinduction of both cell lysis and nucleotide hydrolysis>90 % lysis and DNA degradationStrains are stable to lysis in the absence of phosphate depletion.
Study of the perceived functions and the quality of physical boundaries of public spaces
Authors: G. Saisanath , Gnanasambandam Subbaiyan 
Published: January 2020

Purpose
As an underlying entity in the discourses of privatisation of space, urban security and fear, boundary walls are considered as an impediment to the publicness of public spaces. But, the inevitability and potential of their physical attributes and functions is indicative of the lack of systemic knowledge on how to approach boundary walls, so that they contribute positively to the quality of urban spaces. The paper aims to discuss these issues.

Design/methodology/approach
Since boundary walls are constitutive of physical attributes that are embedded with multiple functions, the contribution of physical boundaries is premised on the interaction between objective and subjective measurements, explored in positive and ambiguous space types. In this study, the quality of physical boundaries is measured by an index and the perceived functions of the physical attributes of boundary walls are measured by a questionnaire survey.

Findings
This study found that positive and ambiguous space types not only affect the quality of physical boundaries but also the perceived functions of the physical attributes of boundary walls. Further, social and visual functions of boundary walls play a significant role in contributing positively to the quality of urban spaces.

Originality/value
By exploring the relation between quality of physical boundaries and their perceived functions, this study extends the meta-understanding of the role of boundary walls.
Explaining the determinants of continual use of mobile financial services
Authors: Adjei Joseph Kwame , Odei-Appiah Solomon , Tobbin Peter Ebo 
Published: January 2020

Purpose
Information system continuance model has been used in a number of studies to explain information system continuance in different contexts. However, very little research attention has been given to continuous use of mobile financial services (MFS). The purpose of this study is to fill this research gap by identifying the main factors that influence the continual use of MFS.

Design/methodology/approach
A sample was randomly taken from MFS registered accounts or mobile wallets. A five-point Likert scale survey was conducted in Ghana. Structural equation modelling was used to test the data. Constructs such as continual use, satisfaction, perceived usefulness and confirmation were adapted from information system continuance model to suit the requirement of MFS. A pilot study was then carried out after the questionnaire was developed to gauge the appropriateness of the survey questions.

Findings
Results from the survey indicated that user satisfaction has the greatest impact on the continual use of mobile financial services. Good agent quality and satisfaction were the second most influential determinant. Satisfaction was, in turn, confirmed to be determined by perceived usefulness. Another important contributor to MFS continual use was found to be perceived ease of use (PEOU) with an impact surprisingly higher than that of perceived usefulness. There was a significant impact of good agent quality on satisfaction, which could be attributed to the characteristics of the technology for the study.

Research limitations/implications
Although a relatively high R2 (71%) was indicated by the proposed model, there is need for additional factors to be identified to improve the ability to predict and explain the continual use of MFS. A longitudinal study would have enhanced the identification of determinants and the understanding of their inter-relationships to influence MFS continual use.

Practical implications
To ensure continual use of MFS, PEOU as identified by the study is important to ensure that customers can use the service with little effort. Good agent quality can promote PEOU in the sense that competent agents can render relevant tutorials to customers’ right after the registration process. This will address a major barrier to continual use, which is the lack of understanding of how MFS operate.

Social implications
This study contributes to ensuring financial inclusion such that the unbanked can have access to financial services and also improve digital inclusion.

Originality/value
The study provides empirical evidence to support the substantive differences between acceptance and continual use behaviours, integrating the constructs of good agent quality and PEOU into our understanding of information system continual use literature. The authors also theorized and evaluated a model of MFS continual use.
When do domestic networks cause accelerated internationalization under different decision-making logic?
Authors: Gil-Barragan Juan M. , Belso-Martínez José A. , Mas-Verdú Francisco 
Published: January 2020

Purpose
Given the unresolved question about which causal conditions contribute to accelerated internationalization among small and medium enterprises (SMEs) from weak institutional environment, this paper aims to combine theoretically relevant antecedents of domestic networks relationships (weak or strong domestic ties) and decision-making logic (effectuation or causation) to explore the configurations that are the most promising for explaining accelerated internationalization.

Design/methodology/approach
This study uses fuzzy-set qualitative comparative analysis (fsQCA) to examine the accelerated internationalization of 33 contrarian cases of SMEs located in weak institutional environment. The data set has been collected through in-depth interviews with managers in Colombia (21 cases) and Peru (12 cases). Building on the findings, an integrative model for accelerated internationalization is presented.

Findings
The authors found that the combination of weak domestic ties and effectuation logic accelerated the internationalization of SMEs with fewer resource constraints. In contrast, strong domestic ties and causation behavior lead to accelerated internationalization of SMEs with greater resource constraints. They propose a model to help enrich the existing literature about the causal configurations for achieving accelerated internationalization in SMEs from weak institutional environment.

Originality/value
The contribution of this study is to provide empirical evidence to address three shortcomings in the literature. First, the mixed results regarding the impact of strong and weak domestic ties and decision-making logic in the accelerated internationalization of SMEs; second, the limited research on domestic networks; and third, the scarce investigation in weak institutional environment, where the emphasis on constrained resources is higher.
Service-learning
Authors: McNatt D. Brian 
Published: January 2020

Purpose
The purpose of this paper is to test whether engaging in course service-learning projects can impact interpersonal oral communication confidence and skill development beyond that of traditional course research projects.

Design/methodology/approach
Three sections of a university management course were randomly assigned to have a service-learning team project, while the other three retained the traditional research team project. All projects were student-generated. Survey data were collected at the beginning of the semester and at the end four months later.

Findings
Results indicated that service-learning produces greater oral communication self-efficacy. For female students, service-learning projects also increased their interpersonal communication self-efficacy and interpersonal communication competence (but not for males).

Research limitations/implications
The sample was limited to students in a management course, service-learning projects were only completed by groups and the study did not examine outcomes beyond four months. Future research could examine outcomes from projects by individuals, and examine what service-learning components create differing results between men and women.

Practical implications
Oral communication confidence can be bolstered through service-learning. Benefits may depend upon participant characteristics (like gender). Inasmuch as different service-learning projects positively impacted oral communication, students can be given flexibility in the kinds of projects they undertake.

Originality/value
This study answered the widespread calls for empirical data to support the claims of service-learning as a beneficial pedagogical tool. The experimental and measurement design overcame the limitations of some previous research. In addition, the study examined the crucial skill area of interpersonal oral communication.