bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-evolutionary Distance Prediction for Flexibility Prediction
Authors: Schwarz Dominik , Georges Guy , Kelm Sebastian , Shi Jiye , Vangone Anna , Deane Charlotte M. 
Published: October 2020

ABSTRACTCo-evolution analysis can be used to accurately predict residue-residue contacts from multiple sequence alignments. The introduction of machine-learning techniques has enabled substantial improvements in precision and a shift from predicting binary contacts to predicting distances between pairs of residues. These developments have significantly improved the accuracy ofde novoprediction of static protein structures. Here we examine the potential of these residue-residue distance predictions to predict protein flexibility rather than static structure. We used DMPfold to predict distance distributions for every residue pair in a set of proteins that showed both rigid and flexible behaviour. Residue pairs that were in contact in at least one reference structure were considered and classified as rigid, flexible or neither. The predicted distance distribution of each residue pair was analysed for local maxima of probability indicating the most likely distance or distances between a pair of residues. The average number of local maxima per residue pair was found to be different between the sets of rigid and flexible residue pairs. Flexible residue pairs more often had multiple local maxima in their predicted distance distribution than rigid residue pairs suggesting that the shape of predicted distance distributions is predictive of rigidity or flexibility of residue pairs.
Autocrine Signaling by Receptor Tyrosine Kinases in Urothelial Carcinoma of the Bladder
Authors: Lee Young H. , Lee Molly M. , De Silva Dinuka M. , Roy Arpita , Wright Cara , Wong Tiffany , Costello Rene , Olaku Oluwole , Grubb Robert L. , Agarwal Piyush K. , Apolo Andrea B. , Bottaro Donald P. 
Published: October 2020

AbstractComprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.
DOT1L primarily acts as a transcriptional repressor in hematopoietic progenitor cells
Authors: Borosha Shaon , Ratri Anamika , Housami Sami M. , Rai Shubham , Ghosh Subhra , Malcom Carrie A. , Chakravarthi V. Praveen , Vivian Jay L. , Fields Timothy A. , Rumi M.A. Karim , Fields Patrick E. 
Published: October 2020

ABSTRACTDOT1L is essential for early hematopoiesis but the precise mechanisms remain largely unclear. The only known function of DOT1L is histone H3 lysine 79 (H3K79) methylation. We generated two mouse models; aDot1L-knockout (Dot1L-KO), and another possessing a point mutation in its methyltransferase domain (Dot1L-MM) to determine the role of its catalytic activity during early hematopoiesis. We observed thatDot1L-KO embryos suffered from severe anemia, whileDot1L-MM embryos showed minimal to no anemia. However,ex vivoculture ofDot1L-MM hematopoietic progenitors (HPCs) exhibited defective development of myeloid and mixed progenitors. DOT1L is a well-recognized, cell-type specific epigenetic regulator of gene expression. To elucidate the mechanisms underlying such diverse hematopoietic properties ofDot1L-KO andDot1L-MM HPCs, we examined their whole transcriptomes. Extensively self-renewing erythroblast (ESRE) cultures were established using yolk sac (YS) cells collected on embryonic day 10.5 (E10.5).Dot1l-KO andDot1l-MM cells expanded significantly less than the wildtype cells and showed slower progression through the cell cycle. Total RNA extracted from the wildtype andDot1l-mutant ESRE cells were subjected to RNA-seq analyses. We observed that the majority (~82%) of the differentially expressed genes (DEGs) were upregulated in both of theDot1L-mutants, which suggests that DOT1L predominantly acts as a transcriptional repressor in HPCs. We also observed that about ~40% of the DEGs were unique to either of the mutant group, suggesting that DOT1L possesses both methyltransferase domain-dependent and -independent functions. We further analyzed Gene Ontology and signaling pathways relevant to the DEGs common to both mutant groups and those that were unique to either group. Among the common DEGs, we observed upregulation of CDK inhibitors, which explains the cell cycle arrest in both of theDot1L-mutant progenitors.
High-throughput transcriptomic analysis of human primary hepatocyte spheroids exposed to per- and polyfluoroalkyl substances (PFAS) as a platform for relative potency characterization
Authors: Rowan-Carroll A. , Reardon A. , Leingartner K. , Gagné R. , Williams A. , Meier M.J. , Kuo B. , Bourdon-Lacombe J. , Moffat I. , Carrier R. , Nong A. , Lorusso L. , Ferguson S.S. , Atlas E. , Yauk C. 
Published: October 2020

AbstractPer- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focussed on four model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at four time-points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS; (2) identify similarities in biological responses; (3) compare PFAS potency through benchmark concentration analysis; and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (i.e., was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.
Numerical Uncertainty in Analytical Pipelines Lead to Impactful Variability in Brain Networks
Authors: Kiar Gregory , Chatelain Yohan , Castro Pablo de Oliveira , Petit Eric , Rokem Ariel , Varoquaux Gaël , Misic Bratislav , Evans Alan C. , Glatard Tristan 
Published: October 2020

AbstractThe analysis of brain-imaging data requires complex processing pipelines to support findings on brain function or pathologies. Recent work has shown that variability in analytical decisions, small amounts of noise, or computational environments can lead to substantial differences in the results, endangering the trust in conclusions1-7. We explored the instability of results by instrumenting a connectome estimation pipeline with Monte Carlo Arithmetic8,9to introduce random noise throughout. We evaluated the reliability of the connectomes, their features10,11, and the impact on analysis12,13. The stability of results was found to range from perfectly stable to highly unstable. This paper highlights the potential of leveraging induced variance in estimates of brain connectivity to reduce the bias in networks alongside increasing the robustness of their applications in the classification of individual differences. We demonstrate that stability evaluations are necessary for understanding error inherent to brain imaging experiments, and how numerical analysis can be applied to typical analytical workflows both in brain imaging and other domains of computational science. Overall, while the extreme variability in results due to analytical instabilities could severely hamper our understanding of brain organization, it also leads to an increase in the reliability of datasets.
Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids
Authors: Elia Uri , Ramishetti Srinivas , Dammes Niels , Bar-Haim Erez , Naidu Gonna Somu , Makdasi Efi , Cohen Ofer , Peer Dan 
Published: October 2020

AbstractThe novel coronavirus SARS-CoV-2 has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple and rapid platform for immunization, and therefore have been employed in recent studies towards the development of a SARS-CoV-2 vaccine. In this study, we present the design of a lipid nanoparticles (LNP)-encapsulated receptor binding domain (RBD) mRNA vaccine. Several ionizable lipids have been evaluatedin vivoin a luciferase mRNA reporter assay, and two leading LNPs formulation have been chosen for the subsequent RBD mRNA vaccine experiment. Intramuscular administration of LNP RBD mRNA elicited robust humoral response, high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. These novel lipids open new avenues for mRNA vaccines in general and for a COVID19 vaccine in particular.
Multiple glacial refugia across northern and southern China and unexpected patterns of spatial genetic diversity inBetula albosinensis: a widespread temperate deciduous tree species
Authors: Liu Lu , Gougherty Andrew V. , Ding Junyi , Li Kun , Wang Wenting , Wang Luwei , Wang Feifei , Wang Nian 
Published: October 2020

AbstractThe central-marginal hypothesis (CMH) predicts high genetic diversity at the species’ geographic centre and low genetic diversity at the species’ geographic margins. However, most studies examining the CMH have neglected potential effect of past climate. Here, we test six hypotheses, representing effects of past climate and contemporary range position, for their ability to explain the spatial patterns of genetic diversity in 37 populations ofBetula albosinensis. Ecological niche modelling (ENM) revealed large and continuous suitable habitats in north, southwest and southeast China during the last glacial maximum (LGM) but a contraction of suitable habitats since the LGM. Pollen records further confirmed the existence of multiple refugia in north and south China. The spatial pattern of genetic diversity (i.e., expected heterozygosity, gene diversity and allele richness) were best explained by distance to the southern edge and distance to the range edge but also showed longitudinal and latitudinal gradients. Hypotheses accounting for the effects of climate (climatic suitability, climatic stability and climatic variability) had comparatively little support. Our findings show partial support for the CMH and illustrates that the existence of multiple LGM refugia, and suggests species abundance and past species movement play a role in shaping genetic diversity across species’ ranges.
Role of TNF-α among inflammatory molecules secreted by injured astrocytes in the modulation ofin vitroneuronal networks
Authors: Lantoine Joséphine , Procès Anthony , Villers Agnès , Halliez Sophie , Buée Luc , Ris Laurence , Gabriele Sylvain 
Published: October 2020

AbstractTraumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide. Despite its high prevalence and extensive efforts to develop neuroprotective therapies, effective treatments for TBI are still limited. Among important neuronal damages, TBI induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. Injured astrocytes respond in diverse mechanisms that result in reactive astrogliosis and are involved in the physiopathological mechanisms of TBI in an extensive and sophisticated manner. The establishment of effective neuroprotective treatments for TBI requires to better understand the complex biochemical interactions between activated astrocytes and neurons that contribute to the secondary injury. To address this challenge, we studiedin vitrothe role of mechanically injured astrocytes on the growth and synaptic connections of cortical neuronal networks of controlled architectures grown on well-defined protein micropatterns. Astrocytes were cultivated on elastic membranes and mechanically activated by stretching cycles. The culture media of healthy or activated astrocytes was then introduced on neuronal networks. We analyzed the neuronal viability, the neurite growth and the synaptic density of neuronal networks to understand the role of the inflammatory molecules secreted by mechanically activated astrocytes. Furthermore, we cultivated neuronal networks during 13 days with different doses of TNF-α in order to decipher its individual contribution among the other cytokines. Here we show that the ratio of tubulin to synapsin area was significantly higher in neuronal networks treated with either 4 or 2 doses of TNF-α, suggesting that TNF-α can promote the tubulin polymerization process. Assuming that TNF-α can bind to either TNFR1 or TNFR2 receptors, which lead respectively to the cell survival or the cell apoptosis, we studied the modulation of the both TNF-α receptors in response to the medium of mechanically activated astrocytes and different doses of TNF-α. Our findings indicate that the amount of both receptors increases with the maturation of the network. In addition, we observed a significant modulation of the amount of TNFR1 and TNFR2 in response to the media of injured astrocytes that leads to a large imbalance between both receptors, suggesting an important role for TNFα-signaling in the physiopathological mechanisms of TBI.
Responding to a major global crisis: the effects of hotel safety leadership on employee safety behavior during COVID-19
Authors: Zhang Jiangchi , Xie Chaowu , Wang Jianying , Morrison Alastair M. , Coca-Stefaniak J. Andres 
Published: October 2020

PurposeThe purpose of this paper is to examine the effect of hotel safety leadership on employee safety behavior during the COVID-19 pandemic, and the mediation role of belief restoration and the moderation role of perceived risk between safety leadership and behavior were also investigated.Design/methodology/approachThe COVID-19 outbreak served as the background for a questionnaire survey of 23 hotels in China with 1,594 valid responses being received. The statistical analysis techniques used were exploratory and confirmatory factor analysis, correlation analysis, structural equation modeling and hierarchical regression.FindingsThe results showed that: hotel safety leadership positively affected employee safety behavior (compliance, participation and adaptation); belief restoration partially mediated the influence of safety leadership on safety behavior; and perceived risk negatively moderated the direct effect and the mediation effect of “safety leadership – belief restoration – safety behavior.”Research limitations/implicationsThe main limitation was that the questionnaires were collected with the same measurement system within a certain period of time (cross-sectional design). Then, future research should test and expand this conceptual model in different crises, business fields, theoretical orientation and cultural backgrounds.Practical implicationsHotels should develop management strategies based on safety leadership and motivate and promote employee safety behavior from the four aspects of safety coaching, care, motivation and control.Originality/valueThis investigation expanded the research on the effectiveness of safety leadership and especially with respect to safety in the hospitality industry during a major global crisis. Also, the research conceptual model and variables contained therein are original contributions to the hospitality research literature.
Social media for entrepreneurship: myth or reality? A structured literature review and a future research agenda
Authors: Secundo Giustina , Del Vecchio Pasquale , Mele Gioconda 
Published: October 2020

PurposeThis paper provides a structured literature review (SLR) about the effects of social media technologies on entrepreneurship activities and processes, to identify relationships, connectivity and interdependencies. The paper offers an outline of the past and the present literature and frames a future research agenda.Design/methodology/approachThe structured literature review has been conducted on 159 journal papers extracted from Scopus, initially submitted to a bibliometric analysis. A final list of 69 papers published in a variety of academic journals specialized in the field of entrepreneurship, information science and business management has been analyzed through a content and bibliometric analysis.FindingsFindings show that literature is really scant, and four research streams have been identified: Social media for entrepreneurial learning and self-employment; social media as tools for entrepreneurial marketing; social media as sources of entrepreneurial opportunities and finally, social media as enablers of networking and entrepreneurial ecosystems.Research limitations/implicationsThe limitations of the study regard the need for more holistic studies, considering both the technological and the social aspects.Practical implicationsThe findings demonstrate the actuality of the research focus and the need of a deep exploration about the role of social media for the different forms of entrepreneurship process. This evidence calls for a holistic and integrated framework.Originality/valueThe originality of the paper resides in a novel SLR with reference to the recent role of social media for entrepreneurship. Despite the increasing literature, the debate in such field is still fragmented and under-researched, offering a promising research field.
An applied study on women's poverty in Turkey in the context of the capability approach
Authors: Kurt Topuz Senem , Erkanlı Hülya 
Published: October 2020

PurposeThe purpose of this study is to present a detailed picture of the poverty conditions of women in Turkey in the context of the capability approach. In other words, it is to analyze their perception of how much women in Turkey can benefit from economic opportunities, political freedoms and social opportunities and to what degree they can have protective security services and transparency assurance.Design/methodology/approachThe field study was conducted in seven cities across Turkey with 741 women. Data from the field study were gathered by using the survey method. A 5-point Likert scale that was developed by the researchers and comprised of 39 statements.FindingsAccording to the scale means of the instrumental freedoms obtained from the survey study, it cannot be claimed that women in Turkey have a completely negative perception of all of the instrumental freedoms. However, if the instrumental freedoms are compared to each other, it is seen that the participants have different perceptions of these instrumental freedoms.Originality/valueThis study basically discusses the issues of women's poverty and freedom in Turkey. In this context, the capability approach by Amartya Sen and capability deprivation; in other words, “being deprived of capabilities”, that is prominent in this approach form the basis of the study. The issue of women's poverty in Turkey is dealt with through deprivations in this study in contrast to the poverty conceptualizations through the individuals' income or expenditure levels.
Meta-analysis in information systems research: method choices and recommendations for future research
Authors: Blut Markus 
Published: October 2020

PurposeThe use of meta-analysis in information systems (IS) research has increased. Because this research domain has matured and an increasing number of empirical studies have become available, meta-analysis is now perceived as a useful approach to synthesize an increasing body of empirical research. The present paper gives an overview of meta-analytical techniques, the evolution of meta-analysis in IS, the focus of these studies and method choices made by authors.Design/methodology/approachThis overview is based on 100 meta-analysis studies published in IS journals. These meta-analytical studies synthesize data from 6,262 empirical studies, and the meta-analyses were published between 1989 and 2020. The studies were coded with regard to 16 major method choices that IS researchers made when conducting meta-analyses.FindingsThis overview describes the key areas of meta-analysis (e.g. strategy and firm performance) and the journals that publish the meta-analysis. This overview also identifies method issues where meta-analyses have improved in recent years as well as issues that require some attention. Scholars receive guidance about good practices in terms of 16 major method choices related to (1) problem formulation, (2) literature search, (3) coding information, (4) analyzing and integrating effect sizes and (5) interpreting results and reporting findings.Originality/valueAddressing the identified method issues helps authors of future meta-analyses to increase the transparency of reporting and the likelihood of getting published. The substantive findings of a meta-analysis also often depend on researchers' method choices. Similar overviews exist for other disciplines, such as marketing and management.