bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the phosphotyrosine binding pocket of Fyn SH2 domain led to the Identification of novel SH2 superbinders
Authors: Li Shuhao , Zou Yang , Zhao Dongping , Yin Yuqing , Song Jingyi , He Ningning , Liu Huadong , Qian Dongmeng , Li Lei , Huang Haiming 
Published: October 2020

AbstractProtein engineering through directed evolution is an effective way to obtain proteins with novel functions with the potential applications as tools for diagnosis or therapeutics. Many natural proteins, largely antibodies as well as some non-antibody proteins, have undergone directed evolution in vitro in the test tubes in the laboratories around the world, resulted in the numerous protein variants with novel or enhanced functions. In this study, we constructed a Fyn SH2 variant library by randomizing the 8 variable residues in its phosphotyrosine (pTyr) binding pocket. Selection of this library by a pTyr peptide from MidT antigen led to the identification of SH2 variants with enhanced affinities to the peptide, compared to the wild type SH2, by EC50 assay. Fluorescent polarization (FP) was then applied to quantify the binding affinity of the newly identified SH2 variants. As a result, three SH2 variants, named V3, V13 and V24, have comparable binding affinities with the previously identified SH2 triple-mutant superbinder (refer to Trm). Biolayer Interferometry (BLI) assay was employed to disclose the kinetics of the binding of these SH2 superbinders, in addition to the wild type SH2, to the phosphotyrosine peptide. The results indicated that all the SH2 superbinders have two-orders increase of the dissociation rate when binding the pTyr peptide while there was no significant change in their associate rates. The previously identified SH2 superbinder Trm as well as the V13 and V24 discovered in this study have cross-reactivity with the sulfotyrosine (sTyr) containing peptide while the wild type SH2 does not. Intriguingly, though binding the pTyr peptide with comparable affinity with other SH2 superbinders, the V3 does not bind to the sTyr peptide, implying it binds to the pTyr peptide with a different pattern from the other superbinders. The newly identified superbinders could be utilized as tools for the identification of pTyr-containing proteins from tissues under different physiological or pathophysiological conditions and may have the potential in the therapeutics.
Metformin strongly affects gut microbiome composition in high-fat diet-induced type 2 diabetes mouse model of both sexes
Authors: Silamiķele Laila , Silamiķelis Ivars , Ustinova Monta , Kalniņa Zane , Elbere Ilze , Petrovska Ramona , Kalniņa Ineta , Kloviņš Jānis 
Published: October 2020

AbstractEffects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mice models, as most of the existing studies have focused on males only.Our study aimed to examine metformin-induced alterations in gut microbiome diversity and composition of high-fat diet-induced type 2 diabetes mouse model, employing a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups. We performed shotgun metagenomic sequencing using DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment.We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species abundances increased. In contrast, no significant changes were observed in control diet-fed mice.We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while, in females, the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.
A novel cost framework reveals evidence for competitive selection in the evolution of complex traits during plant domestication
Authors: Allaby Robin G , Stevens Chris J , Fuller Dorian Q 
Published: October 2020

AbstractMost models of selection incorporate some notion of environmental degradation where the majority of the population becomes less fit with respect to a character resulting in pressure to adapt. Such models have been variously associated with an adaptation cost, the substitution load. Conversely, adaptative mutations that represent an improvement in fitness in the absence of environmental change have generally been assumed to be associated with negligible cost. However, such adaptations could represent a competitive advantage that diminishes resource availability for others and so induces a cost. This type of adaptation in the form of seedling competition has been suggested as a mechanism for increases in seed size during domestication, a trait associated with the standard stabilizing selection model. We present a novel cost framework for competitive selection that demonstrates significant differences in behaviour to environmental based selection in intensity, intensity over time and directly contrasts to the expectations of the standard model. Grain metrics of nine archaeological crops fit a mixed model in which episodes of competitive selection often emerge from shifting optimum episodes of stabilizing selection, highlighting the potential prevalence of the mechanism outlined here and providing a fundamental insight into the factors driving domestication.
Flapjack: a data management and analysis tool for genetic circuit characterization
Authors: Feliú Guillermo Yáñez , Gómez Benjamín Earle , Berrocal Verner Codoceo , Silva Macarena Muñoz , Nuñez Isaac N. , Matute Tamara F. , Medina Anibal Arce , Vidal Gonzalo , Céspedes Carlos Vidal , Dahlin Jonathan , Federici Fernán , Rudge Timothy J. 
Published: October 2020

AbstractCharacterization is fundamental to the design, build, test, learn (DBTL) cycle for engineering synthetic genetic circuits. Components must be described in such a way as to account for their behavior in a range of contexts. Measurements and associated metadata, including part composition, constitute the test phase of the DBTL cycle. These data may consist of measurements of thousands of circuits, measured in hundreds of conditions, in multiple assays potentially performed in different labs and using different techniques. In order to inform the learn phase this large volume of data must be filtered, collated, and analyzed. Characterization consists of using this data to parameterize models of component function in different contexts, and combining them to predict behaviors of novel circuits. Tools to store, organize, share, and analyze large volumes of measurement and metadata are therefore essential to linking the test phase to the build and learn phases, closing the loop of the DBTL cycle. Here we present such a system, implemented as a web app with a backend data registry and analysis engine. An interactive frontend provides powerful querying, plotting and analysis tools, and we provide a REST API and Python package for full integration with external build and learn software. All measurements are associated to circuit part composition via SBOL. We demonstrate our tool by characterizing a range of genetic components and circuits according to composition and context.
Investigating epithelial-mesenchymal heterogeneity of tumors and circulating tumor cells with transcriptomic analysis and biophysical modeling
Authors: Bocci Federico , Mandal Susmita , Tejaswi Tanishq , Jolly Mohit Kumar 
Published: October 2020

AbstractIntroductionCellular heterogeneity along the Epithelial-Mesenchymal Plasticity (EMP) spectrum is a paramount feature observed in tumors and circulating tumor cells (CTCs). High-throughput techniques now offer unprecedented details on this variability at a single-cell resolution. Yet, there is no current consensus about how EMP in tumors propagates to that in CTCs. To investigate the relationship between EMP associated heterogeneity of tumors and that of CTCs, we integrated transcriptomic analysis and biophysical modeling.MethodsWe apply three EMT (Epithelial-Mesenchymal Transition) scoring metrics to multiple tumor samples and CTC datasets from several cancer types. Moreover, we develop a biophysical model that couples EMT associated phenotypic switching in a primary tumor with cell migration. Finally, we integrate EMT transcriptomic analysis andin silicomodeling to evaluate the predictive power of several measurements of tumor aggressiveness, including tumor EMT score, CTC EMT score, fraction of CTC clusters found in circulation, and CTC cluster size distribution.ResultsAnalysis of high-throughput datasets reveals a pronounced heterogeneity without a well-defined relation between EMT traits in tumors and CTCs. Moreover, mathematical modeling predicts different phases where CTCs can be less, equally, or more mesenchymal than primary tumor depending on the dynamics of phenotypic transition and cell migration. Consistently, various datasets of CTC cluster size distribution from different cancer types are fitted onto different regimes of the model. By further constraining the model with experimental measurements of tumor EMT score, CTC EMT score, and fraction of CTC cluster in bloodstream, we show that none of these assays alone can provide sufficient information to predict the other variables.ConclusionsBy integrating analysis of single cell gene expression andin silicomodeling, we propose that the relationship between EMT progression in tumors and CTCs can be variable, and in general, predicting one from the other may not be as straightforward as tacitly assumed.
Characterizing the demographic history and prion protein variation to infer susceptibility to chronic wasting disease in a naïve population of white-tailed deer (Odocoileus virginianus)
Authors: Haworth Sarah E , Nituch Larissa , Northrup Joseph M , Shafer Aaron BA 
Published: October 2020

AbstractAssessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human-dominated landscapes, often with contrasting effects. White-tailed deer (deer) are expanding in the northern part of their range following decreasing winter severity and increasing forage availability. Chronic wasting disease (CWD), a prion disease affecting cervids, is likewise expanding and represents a major threat to deer and other cervids. We obtained tissue samples from free-ranging deer across their native range in Ontario, Canada which has yet to detect CWD in wild populations of cervids. We used high-throughput sequencing to assess neutral genomic variation, and variation in the PRNP gene that is partly responsible for the protein misfolding when deer contract CWD. Neutral variation revealed a high number of rare alleles and no population structure, and demographic models suggested a rapid historical population expansion. Allele frequencies of PRNP variants associated with CWD susceptibility and disease progression were evenly distributed across the landscape and consistent with deer populations not infected with CWD. We then estimated the selection coefficient of CWD, with simulations showing an observable and rapid shift in PRNP allele frequencies that coincides with the start of a novel CWD epidemic. Sustained surveillance of genomic and PRNP variation can be a useful tool for CWD-free regions where deer are managed for ecological and economic benefits.
Molecular mechanisms of LC3-associated phagocytosis in the macrophage response toParacoccidioidesspp
Authors: de Oliveira Getúlio Pereira , de Sousa Herdson Renney , de Melo Gorgonha Kaio César , dos Santos Borges Tatiana Karla , Rangel Kellyanne Teixeira , Fabricant Scott , Gustavo Fernanda Cristina Koser , Friaça Lucas Fraga , Neto Angelo Rossi , Hurtado Fabián Andrés , Paes Hugo Costa , Casadevall Arturo , Silva-Pereira Ildinete , Albuquerque Patrícia , Felipe Maria Sueli Soares , Nicola André Moraes 
Published: October 2020

AbstractParacoccidiomycosis is a systemic fungal infection that is endemic in Latin America. The etiologic agents are thermodimorphic fungi from theParacoccidiodesgenus, which are facultative intracellular parasites of macrophages. LC3-associated phagocytosis (LAP), a noncanonical form of autophagy, is important in the immune response to similar pathogens, so we sought to determine the role LAP plays in the macrophage response toParacoccidioidesspp. By immunofluorescence, we found that LC3 was recruited to phagosomes containingParacoccidioidesspp. in both RAW264.7 and J774.16 cell lines and in bone marrow-derived macrophages. Interference with autophagy using RNAi againstATG5reduced the antifungal activity of J774.16 cells, showing that LC3 recrutiment is important for proper control of the fungus by macrophages. Finally, we used pharmacological Syk kinase and NAPH oxidase inhibitors, which inhibit signalling pathways necessary for macrophage LAP againstAspergillus fumigatusandCandida albicans, to dissect part of the signaling pathways that trigger LAP againsParacoccidioidesspp. Interestingly, these inhibitors did not decrease LAP againstP. brasiliensis, possibly due to differences in the fungal cell surface compositions. These observations suggest a potential role for autophagy as target for host-directed paracoccidioidomycosis therapies.
“My little piece of the planet”: the multiplicity of well-being benefits from allotment gardening
Authors: Dobson Miriam Clare , Reynolds Christian , Warren Philip H. , Edmondson Jill L. 
Published: October 2020

PurposeParticipation in urban horticulture (UH) is increasing in popularity, and evidence is emerging about the wide range of social and environmental benefits “grow your own” can also provide. UH can increase mental and physical well-being, as well as improve nature connectedness, social capital and community cohesion.Design/methodology/approachThis study focusses on allotments, which is one of the dominant forms of UH that takes place in the United Kingdom. 163 volunteers in England and Wales participated in keeping a year-long allotment diary as part of a citizen science project investigating activities on allotment gardens. This study examines the unprompted comments that 96 of these gardeners offered as observations when visiting their allotment plots.FindingsParticipants recorded high levels of social and community activities including the sharing of surplus food produce, knowledge exchange, awareness and interaction with wildlife, emotional connection to their allotment, appreciation of time spent outside and aesthetic delight in the natural world around them.Originality/valueAt a time when waiting lists for allotment plots in the United Kingdom are on the rise, and allotment land is subject to multiple pressures from other forms of development, this study demonstrates that these spaces are important sites not only for food production but also health, social capital and environmental engagement.
Barriers to integrating building information modelling (BIM) and lean construction practices on construction mega-projects: a Delphi study
Authors: Evans Martin , Farrell Peter 
Published: October 2020

PurposeThe construction industry encounters substantial challenges in its evolution towards sustainable development and in the adoption of building information modelling (BIM) technology and lean construction (LC) practices on construction mega-projects. This research aims to investigate the critical barriers encountered by key construction stakeholders in their efforts to integrate BIM and LC in the construction mega-projects.Design/methodology/approachA two-round Delphi survey shaped the foundation of aggregating consensus between an expert panel that examined a set of 28 barriers resulting from a detailed analysis of the extant literature. Descriptive and inferential statistical tests were exploited for data analysis, and interrater agreement analysis was used to elaborated and validate results.FindingsThe research concluded that the key barriers by descending order of significance are lack of mandatory BIM and LC industry standards and regulations by the government, resistance of the industry to change from traditional practices to LeanBIM, high cost of software licenses and training and running of BIM.Originality/valueThe research findings and the proposed mitigation strategy will enhance the application of BIM and LC practices in construction mega-projects and allow project key stakeholders to place emphasis on tackling the crucial challenges and barriers identified in this research.
Exploring flexible home arrangements – an interview study of workers who live in vans
Authors: Duff Angus J. , Rankin Scott B. 
Published: October 2020

PurposeThe purpose of this study is to understand the lived experience of workers who live in vans to explore how work and non-work interact when one's living environment is mobile.Design/methodology/approachIn this qualitative study, semi-structured interviews were carried out with 18 participants. Thematic analysis of interview transcripts, coded while listening to each interview recording, provided a rich account of the interaction of work and non-work life domains.FindingsSeveral themes were identified, including seeing the van as a home, hidden or disclosed identity stemming from living in a van, financial freedom, career freedom and work/non-work synchronization. Overall, findings suggest that flexible home arrangements, the relocation of one's home to adapt to work, aligned work and non-work domains to positively impact their overall work and non-work satisfaction, providing career freedom and expanded career opportunities.Research limitations/implicationsThe understanding of workers who live in vans broadens one’s understanding of mobile work and the work/non-work interface, providing insight into the dual alignment of work and home to accommodate each other, which the authors term work/non-work synchronization.Originality/valueThis is one of the first studies to consider van living from a work and career perspective and for the first time conceptualizes the notion of flexible home arrangements.
Testing the precautionary argument after the Lucky Dragon incident
Authors: Dörries Matthias 
Published: October 2020

PurposeThis paper uses a historical case study, the controversy over the possibility of climatic extremes caused by hydrogen bomb tests on Pacific Ocean atolls during the 1950s, to show how, in a context of few scientific data and high uncertainty, political affiliations and public concerns shaped two types of argumentation, the “energy” and the “precautionary” arguments.Design/methodology/approachSystematic analysis of publications 1954–1956: scientific and semiscientific articles, publications of C.-N. Martin and contemporary newspaper articles, especially from the Asia–Pacific region.FindingsFirst, epistemological and scientific reasoning about the likelihood of extreme natural events aligned to political convictions and pressure. Second, a geographical and social distribution of arguments: the relativizing “energy argument” prevailed in English-language scientific journals, while the “precautionary argument” dominated in popular journals and newspapers published worldwide. Third, while the “energy argument” attained general scientific consensus within two years, it lost out in the long run. The proponents of the “precautionary argument” raised relevant research questions that, though first rejected in the 1950s, later exposed the fallacies of the “energy argument” (shown for the case of the climatologist William W. Kellogg).Originality/valueIn contrast to the existing secondary literature, this paper presents a balanced view of the weaknesses and strengths of two lines of arguments in the 1950s. Further, this historical study sheds light on how once-discarded scientific theories may ultimately be reconsidered in a completely different political and scientific context, thus justifying the original precautionary argument.
The reception and use of John Dewey's educational ideas by Hu Shi in the Early Republic of China
Authors: Zhao Kang 
Published: October 2020

PurposeSome studies have claimed that Chinese thinker Hu Shi (or Hu Shih) received and responded to John Dewey's educational ideas only at a theoretical level and did little for education at a practical level. This paper reexamines Hu's reception of Dewey's ideas with a focus on how he used those ideas to solve China's educational and social problems during the late 1910s and 1920s.Design/methodology/approachThis paper draws upon what Schriewer (2012) has called “theories of reception.” Rather than focusing on the international dissemination of ideas and knowledge, this approach emphasizes the reception of foreign ideas from the perspective and needs of the receiver, interpreter and/or reader who apprehends such ideas within a particular socio–cultural context.FindingsThis paper finds that Hu not only received — and examined — Dewey's educational ideas in a systematic way, but also used them pragmatically to reform China's systems of education as part of the New Culture Movement after 1919.Originality/valueThis research offers a new understanding of Hu's reception of Dewey's educational ideas. It shows that Hu was not merely a “thinker” in the field of education but also a “doer” who sought to apply Dewey's ideas in practice. This new view allows us to reevaluate Hu's role in the modernization of Chinese education.
Antecedents of corporate reputation with employees in higher education institutions: a systematic review
Authors: Rashid Sufyan , Mustafa Hasrina 
Published: October 2020

PurposeThe purpose of this paper is to provide a systematic review of studies on antecedents of the corporate reputation of higher education institutions (HEIs) from the perspectives of employeesDesign/methodology/approachThe approach is an examination of previous literature on antecedents of corporate reputation in HEIs, published between 2010 and 2020.FindingsThe findings show that general and specific factors of corporate reputation in HEIs are being employed as strategic tools to survive the competitive nature of the higher education landscape.Originality/valueFactors of corporate reputation in HEIs from the perspectives of employees are an understudied area with little academic literature available.