bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic code expansion in the engineered organism Vmax X2: High yield and exceptional fidelity
Authors: Santiago Sebasthian , Ad Omer , Shah Bhavana , Zhang Zhongqi , Zhang Xizi , Chatterjee Abhishek , Schepartz Alanna 
Published: June 2021

AbstractWe report that the recently introduced commercial strain of V. natriegens (Vmax X2) supports robust unnatural amino acid mutagenesis, generating exceptional yields of soluble protein containing up to 5 non-canonical α-amino acids (ncAA). The isolated yields of ncAA-containing superfolder green fluorescent protein (sfGFP) expressed in Vmax X2 are up to 25-fold higher than those achieved using commercial expression strains (Top10 and BL21) and more than10-fold higher than those achieved using two different genomically recoded E. coli strains that lack endogenous UAG stop codons and release factor 1 and have been optimized for improved fitness and preferred growth temperature (C321.ΔA.opt and C321.ΔA.exp). In addition to higher yields of soluble protein, Vmax X2 cells also generate proteins with significantly lower levels of mis-incorporated natural α-amino acids at the UAG-programmed position, especially in cases where the ncAA is an imperfect substrate for the chosen orthogonal aminoacyl tRNA synthetase (aaRS). This increase in fidelity implies that use of Vmax X2 cells as the expression host can obviate the need for time-consuming directed evolution experiments to improve specific activity of highly desirable but imperfect ncAA substrates.
Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines
Authors: Riccio Federica , Micarelli Elisa , Secci Riccardo , Giuliani Giulio , Vumbaca Simone , Massacci Giorgia , Castagnoli Luisa , Fuoco Claudia , Cesareni Gianni 
Published: June 2021

AbstractRepurposing of drugs for new therapeutic use has received considerable attention for its potential to reduce time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to induce differentiation of leukemic cells. As Acute Myeloid Leukemia (AML) is the result of a block in myeloid differentiation, finding new drugs that are capable of inducing blast terminal maturation is considered a valuable strategy. We used data from the Connectivity Map (CMap) to identify drugs that could be repositioned for their potential to activate transcription factors that mediate myeloid differentiation. Compounds promoting the activation of transcription factors that play a positive role in myeloid differentiation were considered candidate pro-differentiation drugs. This approach yielded a list of chemicals ranked according to the potential to activate transcription factors that induce differentiation of leukemic progenitor cells. Drugs that are already used in differentiation therapy, such as for instance all-trans retinoic acid (ATRA) are in the top positions of this ranked list. To validate our strategy, we tested thein vitrodifferentiation potential of 22 candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, ranking high in the inferred list, were confirmed to induce significant differentiation of HL-60. Some of these compounds are known to trigger the DNA damage response, thus identifying this process as a target to modulate myeloid differentiation. These results underscore the potential of our approach to accelerate the drug discovery process. The method that we have developed is highly versatile and it can be adapted to different drug repurposing projects.
Rapid Ensemble Measurement of Protein Diffusion, Probe Blinking and Photobleaching Dynamics in the Complex Cellular Space
Authors: Sehayek Simon , Yi Xiyu , Weiss Shimon , Wiseman Paul W. 
Published: June 2021

AbstractWe present a fluorescence fluctuation image correlation analysis method that can rapidly and simultaneously measure the diffusion coefficient, photoblinking rates, and fraction of diffusing particles of fluorescent molecules in cells. Unlike other image correlation techniques, we demonstrated that our method could be applied irrespective of a non-uniformly distributed, immobile blinking fluorophore population. This allows us to measure blinking and transport dynamics in complex cell morphologies, a benefit for a range of super-resolution fluorescence imaging approaches that rely on probe emission blinking. Furthermore, we showed that our technique could be applied without directly accounting for photobleaching. We successfully employed our technique on several simulations with realistic EMCCD noise and photobleaching models, as well as on Dronpa-C12 labeled beta-actin in living NIH/3T3 and HeLa cells. We found that the diffusion coefficients measured using our method were consistent with previous literature values. We further found that photoblinking rates measured in the live HeLa cells varied as expected with changing excitation power.
A double-hit in vivo model of GBA1 viral microRNA-mediated downregulation and human alpha-synuclein overexpression demonstrates nigrostriatal degeneration
Authors: Polissidis Alexia , Nikolopoulou Georgia , Koronaiou Effrosyni , Nikatou Maria , Viel Catherine , Boyongo Marios , Pablo Sardi S. , Xilouri Maria , Vekrellis Kostas , Stefanis Leonidas 
Published: June 2021

AbstractPreclinical and clinical studies support a strong association between mutations in the GBA1 gene that encodes β-glucocerebrosidase (GCase) (EC 3.2.1.45; glucosylceramidase beta) and Parkinson’s disease (PD). Alpha-synuclein (AS), a key player in PD pathogenesis, and GBA1 mutations may independently and synergistically cause lysosomal dysfunction and thus, embody clinically well-validated targets of the neurodegenerative disease process in PD. However, double-hit in vivo models, recapitulating pathological features of PD that can be used to dissect the nature of the complex relationship between GCase and AS on the nigrostriatal axis, the region particularly vulnerable in PD, are direly needed. To address this, we implemented a bidirectional approach in mice to examine the effects of: 1) GCase overexpression (wildtype and mutant N370S) on endogenous AS levels and 2) downregulation of endogenous GCase combined with AS overexpression. Striatal delivery of viral-mediated GCase overexpression revealed minimal effects on cortical and nigrostriatal AS tissue levels and no significant effect on dopaminergic system integrity. On the other hand, microRNA (miR)-mediated GBA1 downregulation (miR GBA), combined with virus-mediated human AS overexpression (+AS), yields decreased GCase activity in the cortex, mimicking levels seen in GBA1 heterozygous carriers (30-40%), increased astrogliosis and microgliosis, decreased striatal dopamine levels (50% compared to controls) and loss of nigral dopaminergic neurons (~33%)-effects that were all reversible with miR rescue. Most importantly, the synergistic neurodegeneration of miR GBA+AS correlated with augmented AS accumulation and extracellular release in the striatum. Collectively, our results suggest that GCase downregulation alone is not sufficient to recapitulate key pathological features of PD in vivo, but its synergistic interplay with AS, via increased AS levels and release, drives nigrostriatal neurodegeneration. Furthermore, we demonstrate a novel double-hit model that can be used to identify putative mechanisms driving PD pathophysiology and can be subsequently used to test novel therapeutic approaches.
AtPQT11, a P450 enzyme, detoxifies paraquat via N-demethylation
Authors: Huang Yi-Jie , Huang Yue-Ping , Xia Jin-Qiu , Fu Zhou-Ping , Chen Yi-Fan , Huang Yi-Peng , Ma Aimin , Hou Wen-Tao , Chen Yu-Xing , Qi Xiaoquan , Gao Li-Ping , Xiang Cheng-Bin 
Published: June 2021

AbstractParaquat is one of the most widely used nonselective herbicides in agriculture. Due to its wide use, paraquat resistant weeds have emerged and is becoming a potential threat to agriculture. The molecular mechanisms of paraquat resistance in weeds remain largely unknown. Physiological studies indicated that the impaired translocation of paraquat and enhanced antioxidation could improve paraquat resistance in plants. However, the detoxification of paraquat via active metabolism by plants has not been reported to date. Here we report that an activated expression of At1g01600 encoding the P450 protein CYP86A4 confers paraquat resistance as revealed by the gain-of-function mutant paraquat tolerance 11D (pqt11D), in which a T-DNA with four 35S enhancers was inserted at 1646 bp upstream the ATG of At1g01600. The paraquat resistance can be recapitulated in Arabidopsis wild type by overexpressing AtPQT11 (At1g01600), while its knockout mutant is hypersensitive to paraquat. Moreover, AtPQT11 also confers paraquat resistance in E. coli when overexpressed. We further demonstrate that AtPQT11 has P450 enzyme activity that converts paraquat to N-demethyl paraquat nontoxic to Arabidopsis, therefore detoxifying paraquat in plants. Taken together, our results unequivocally demonstrate that AtPQT11/ CYP86A4 detoxifies paraquat via active metabolism, thus revealing a novel molecular mechanism of paraquat resistance in plants and providing a means potentially enabling crops to resist paraquat.
The Influence of Public Health Faculty on College and University Plans during the COVID-19 Pandemic
Authors: Johnson David A. , Cahill Meredith , Choate Sara , Roelfs David , Walsh Sarah E. 
Published: June 2021

AbstractThe purpose of this study was to determine whether the institutional presence of public health faculty within colleges and universities influenced operational plans for the fall semester of 2020. Using cross-sectional data collected by the College Crisis Initiative of Davidson College, six levels of instructional modalities (ranked from least to most restrictive) were compared between Council on Education of Public Health (CEPH)-accredited and non-CEPH-accredited 4-year institutions. Institutions with CEPH-accredited schools and programs were more likely to select some restrictive teaching modalities: 63.8% more likely to use hybrid/hyflex or more restrictive and 66.9% more likely to be primarily online (with some in person) or more restrictive. However, having CEPH-accredited programs did not push institutions to the most restrictive modalities. COVID-19 cases in county, enrollment, and political affiliation of the state governor were also found to influence instructional modality selection. While any ecological study has certain limitations, this study demonstrates that college and university fall plans appear to have been influenced by the presence of CEPH-accredited schools and programs of public health, and/or the input of their faculty. The influence of relevant faculty expertise on institutional decision-making can help inform college and university responses to future crises.
De-novo draft genome sequence of Crocus Sativus L, Saffron, a golden condiment
Authors: Ambardar Sheetal , Vakhlu Jyoti , Sowdhamini Ramanathan 
Published: June 2021

AbstractCrocus sativus L, saffron is the highest priced but low yielding plant of medicinal and culinary importance. Despite its economic status, the omic information on this plant is very scarce, with only a couple of transcriptomics and epigenetic studies. In the present study, the draft genome sequence of C. sativus has been assembled using Illumina sequencing. In fact, this is the first genome sequence from any member of family Iridaceae. Genome size of C. sativus was estimated to be 3.5 Gb and the draft genome is 3.01 Gb long with 84.24% genome coverage. In total, 8,62,275 repeats and 9,64,231 SSR markers have been identified. A total of 53,546 functional genes were annotated, out of which, 43,649 proteins were associated with GO annotation. 5726 proteins were identified as transcription factors, with MYB & MYB related family proteins being more abundant. Orthology analysis of C. sativus with 3 different monocot species of the same plant order and rice (model monocot plant) revealed 7328 proteins clusters to be conserved in all the five plant species, whereas 2510 proteins cluster were unique to C. sativus only. 10,912 unigenes of C. sativus were mapped to 387 KEGG pathways of monocot. The genes involved in the pathway of apocarotenoids biosynthesis (crocin, crocetin, picrocrocin, and safranal) were present in the draft genome.
Quantitative phase measurements of human cell nuclei using X-ray ptychography
Authors: Schwenke Jorg , Yusuf Mohammed , Shemilt Laura A. , Wagner Ulrich , Sajid Atiqa , Morrison Graeme R. , Zhang Fucai , Parsons Aaron , Rau Christoph , Robinson Ian K. 
Published: June 2021

The human cell nucleus serves as an important organelle holding the genetic blueprint for life. In this work, X-ray ptychography was applied to assess the masses of human cell nuclei using its unique phase shift information. Measurements were carried out at the I13-1 beamline at the Diamond Light Source that has extremely large transverse coherence properties. The ptychographic diffractive imaging approach allowed imaging of large structures that gave quantitative measurements of the phase shift in 2D projections. In this paper a modified ptychography algorithm that improves the quality of the reconstruction for weak scattering samples is presented. The application of this approach to calculate the mass of several human nuclei is also demonstrated.
Work stressors and job outcomes: an empirical investigation of frontline service employees in the Indian hospitality industry
Authors: Pradhan Sajeet 
Published: June 2021

PurposeThe study aims to investigate the relationship between work stressors (abusive supervision and dysfunctional customer behaviour) and several job outcomes such as service sabotage, job satisfaction and intention to quit among frontline employees in the Indian hospitality industry. It also explores the mediating role of emotional exhaustion explaining the indirect effect between the work stressors and the job outcomes.Design/methodology/approachThis is a multi-wave (data collected at two time points) cross-sectional survey study. In order to test the study hypotheses, the study draws responses from frontline employees working in several hotels and restaurants in India. The final sample of 274 was analysed using SmartPLS and Statistical Product and Service Solutions (SPSS).FindingsResults report that both the work stressors were significantly related to the job outcomes in the direction suggested in the literature. Also, the indirect effect between the work stressors and the job outcomes via emotional exhaustion were found to be significant.Originality/valueThe present study makes two unique contributions to the extant literature; first, it conceptualizes and empirically tests the pernicious impact of multiple work stressors like abusive supervisor and dysfunctional customer behaviour on the job outcomes of frontline hospitality industry employees. Second, it is the only study to investigate the relationship between the two work stressors and service sabotage in the Indian hospitality industry.
Female entrepreneurs in a time of crisis: evidence from Ireland
Authors: Stephens Simon , Cunningham Isobel , Kabir Yousra 
Published: June 2021

Purpose
The purpose of this paper is to develop an understanding of the impact that a crisis such as that created by COVID-19 has on entrepreneurs. The authors focus on female entrepreneurs and their ability and propensity to continue their entrepreneurial journey.

Design/methodology/approach
For each respondent (n = 113), data was collected using an online survey. The survey was distributed in April 2020 during a nationwide lockdown and again in September 2020 as the economy reopened. In completing the survey, respondents were asked a series of multiple-choice questions and a series of open-ended questions.

Findings
The authors present data characterizing the female entrepreneurs, their experience during a time of crisis and the enablers and disablers to the continuation of their entrepreneurial journey. The key findings that emerge from this study include the resilience of the female entrepreneurs, their willingness to contribute to community-based organizations during a crisis and their desire to seek and receive support from their peers.

Originality/value
The findings from this study provide novel insights with regard to the resources and strategies used by female entrepreneurs during a time of crisis. The data was collected during two periods of great uncertainty for the entrepreneurs and at times when their availability was extremely limited.
Network reliance and entrepreneurial performance, the role of external networking behaviour and entrepreneurial orientation: the case of rural farmer-entrepreneurs
Authors: Udimal Thomas Bilaliib , Liu E. , Lou Mingcan 
Published: June 2021

PurposeThe purpose of this study is to specifically look at the relationship between reliable network reliance and entrepreneurial performance.Design/methodology/approachTo help achieve the study objective, 450 rural farmer-entrepreneurs from Jiangsu, Anhui, Guangxi and Zhejiang Provinces were randomly selected. The study concentrated mainly on entrepreneurs who have engaged in entrepreneurial activities the past five or more years.FindingsThis study’s findings show that network reliance has direct and indirect effects on entrepreneurial performance through external networking behaviour. The result further shows that external networking behaviour partially mediates the relationship between network reliance and entrepreneurial performance. On the moderation effect on entrepreneurial orientation (EO), the result reveals that it strengthens the relationship between external networking behaviour and entrepreneurial performance. The result shows that EO has a direct effect on entrepreneurial performance. The paper introduces behavioural component of network to entrepreneurial performance. The study concludes that external networking behaviour of entrepreneurs is key in entrepreneurship as it improves relationships among actors and thereby translating into an improved performance.Originality/valueThe paper brings to light the need to reconsider extension education by including elements of networking to enable rural entrepreneurs derive full benefits of their entrepreneurial ventures.
An empirical study of the performance of weather routing service in the North Pacific Ocean
Authors: Tsai Chaur-Luh , Su Dong-Taur , Wong Chun-Pong 
Published: June 2021

PurposeThe objective of this research is to examine the performance of weather routing service in the North Pacific Ocean based on a global container shipping company.Design/methodology/approachThe data comprise two passages: one that departs from the port of Taipei to the port of Los Angeles (TPE-LAX) and another that departs from the port of Tacoma to the port of Kaohsiung (TCM-KSG). A weather routing service was utilized to compare the differences of the distance, sailing time and fuel consumed among different voyages.FindingsResults indicated that the average speed of vessel in winter is faster than in summer. The vessels consumed much more fuel in the winter than they did in the summer. In terms of the distance of the passage, the results show that the ships' sailing distance across the North Pacific Ocean in the summer was shorter than it was in the winter.Research limitations/implicationsDue to the difficultly of practical data collection, relatively few sailing records were employed in this study. It is suggested that additional sailing records should be collected, which adopt weather routing recommendations, to more comprehensively analyze sailing performance in future research.Practical implicationsThe study's findings offer valuable guidance to different stakeholders in the maritime industry (e.g. seafarers, marine hull and machinery companies, Protection and Indemnity Club (P&I), ocean container carriers and freight forwarders) to clarify their responsibilities in order to achieve desired sailing outcomes.Originality/valueTo the best of the authors' knowledge, the current study is the first research to utilize practical sailing data to provide objective evidence of sailing performance based on a weather routing service, which can assist various stakeholders to make optimal decisions.
Blogs, identity, stigma and scars: the legacy of self-injury
Authors: Kendall Nadine , MacDonald Caylee , Binnie James 
Published: June 2021

Purpose
This paper aims to explore the experience of living with scars from self-injury; how people who self-injure (SI) make meaning of their scars and how these scars are a part of the identity construction process.

Design/methodology/approach
It is observed that 60 entries, from 25 online narrative blogs detailing the experience of living with self-injury scars, were analyzed using a contextualized thematic analysis informed by an embodied perspective.

Findings
The analysis generated two dominant themes: temporal aspects of identity; and social stigma and scars.

Originality/value
Far-reaching consequences of self-injury scars on the daily lives of people who SI was found. This included a person’s posture, clothing, choices of career, inclusion in family life, leisure activities and relationships; all of which have corollaries in emotional and psychological well-being. Scars were found to be self-narrative with particular salience given to how scars represented healing. Novel findings included the central role scars played in the resistance of self-injury stigma.
Entrepreneurship education: systematic literature review and future research directions
Authors: Mohamed Nasra Ahmed , Sheikh Ali Ali Yassin 
Published: June 2021

PurposeThe purpose of the study is to further understanding of entrepreneurship education, highlighting current trends and directions for further research.Design/methodology/approachThis paper used systematic literature review of published articles to collect, evaluate, and interpret entrepreneurship education literature from selected databases between 2009 and 2019. The study reviewed 90 articles from the entrepreneurship education literature. There are several different topics that have been analyzed; with the most researched topic being analyzed was focusing on entrepreneurship education development.FindingsEntrepreneurship education programs have become an increasingly important focus of attention in recent years. This paper deeply investigates the literature on entrepreneurship education to help entrepreneurship education decision makers to develop better solutions.Research limitations/implicationsIt must be noted that this study has some limitations, which suggest avenues for further research. In reviewing the articles, the study used only four databases and only considered papers published between 2009 and 2019. Other studies may include more databases and a longer time frame.Originality/valueRegarding the theories most used in the reviewed articles, TPB and social learning theory (SLT) were most used in relation to entrepreneurship education. This shows that researchers were focusing on the influence of entrepreneurship education in relation to the entrepreneurial intention, behavior and attitude of the individuals.