bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geldanamycin inhibits Jumonji histone lysine demethylase KDM4 and targets chimeric transcription factor PAX3-FOXO1
Authors: Abu-Zaid Ahmed , Singh Shivendra , Lin Wenwei , Low Jonathan , Abdolvahabi Alireza , Cooke Bailey , Bowling John , Vaithiyalingam Sivaraja , Fang Jie , Currier Duane , Yun Mi-Kyung , AlTahan Alaa , Fernando Dinesh M. , Maier Julie , Tillman Heather , Bulsara Purva , Lu Zhaohua , Das Sourav , Li Zhenmei , Young Brandon , Lee Richard , Rankovic Zoran , White Stephen , Davidoff Andrew M. , Chen Taosheng , Yang Jun 
Published: December 2019

AbstractHistone lysine demethylases (KDMs) are emerging as therapeutic targets in cancer. Development of potent KDM inhibitors may provide additional options for epigenomics-oriented therapies. Using a Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) functional demethylation assay, in combination with a high-content immunofluorescence imaging phenotypic screen, Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance mass spectrometry (MALDI-FTICR MS) and Amplified Luminescent Proximity Homogeneous Assay (ALPHA), we identified geldanamycin, an inhibitor of heat shock protein 90 (Hsp90), as a novel inhibitor of JmjC-domain containing demethylases such as KDM4B. We further found that geldanamycin can destabilize the PAX3-FOXO1 fusion oncoprotein, an Hsp90 client, which is a driver of clinically unfavorable alveolar rhabdomyosarcoma (aRMS). We then hypothesized that dual inhibition of PAX3-FOXO1 and epigenetic modifiers of aRMS would have synergistic antitumor activity. We repurposed the geldanamycin analog 17-DMAG to target aRMS and found that 17-DMAG significantly delays tumor growth, extends survival in xenograft mouse models, and inhibits expression of PAX3-FOXO1 targets and multiple oncogenic pathways including MYC, E2F and NOTCH. In addition, the combination of 17-DMAG with conventional chemotherapy or the bromodomain inhibitor JQ1 significantly enhances therapeutic efficacy. In summary, we have identified geldanamycin and 17-DMAG as dual KDM/Hsp90 inhibitors and 17-DMAG is efficacious against PAX3-FOXO1-driven rhabdomyosarcoma.
Evidence for dual targeting of Arabidopsis plastidial glucose-6-phosphate transporter GPT1 to peroxisomes via the ER
Authors: Baune Marie-Christin , Lansing Hannes , Fischer Kerstin , Meyer Tanja , Charton Lennart , Linka Nicole , von Schaewen Antje 
Published: December 2019

ABSTRACTFormer studies on Arabidopsis glucose-6-phosphate/phosphate translocator isoforms GPT1 and GPT2 reported viability ofgpt2mutants, however an essential function for GPT1, manifesting as a variety ofgpt1defects in the heterozygous state during fertilization/seed set. Among other functions, GPT1 is important for pollen and embryo-sac development. Since previous work on enzymes of the oxidative pentose phosphate pathway (OPPP) revealed comparable effects, we investigated whether GPT1 might dually localize to plastids and peroxisomes. In reporter fusions, GPT2 was found at plastids, but GPT1 also at the endoplasmic reticulum (ER) and around peroxisomes. GPT1 contacted oxidoreductases and also peroxins that mediate import of peroxisomal membrane proteins from the ER, hinting at dual localization. Reconstitution in yeast proteoliposomes revealed that GPT1 preferentially exchanges glucose-6-phosphate for ribulose-5-phosphate. Complementation analyses of heterozygousgpt1plants demonstrated that GPT2 is unable to compensate for GPT1 in plastids, whereas genomicGPT1without transit peptide (enforcing ER/peroxisomal localization) increasedgpt1transmission significantly. Since OPPP activity in peroxisomes is essential during fertilization, and immuno-blot analyses hinted at unprocessed GPT1-specific bands, our findings suggest that GPT1 is indispensable at both plastids and peroxisomes. Together with the G6P-Ru5P exchange preference, dual targeting explains why GPT1 exerts functions distinct from GPT2 in Arabidopsis.One sentence summaryIn contrast to plastidial GPT2, GPT1 exhibits slightly different exchange preferences and alternatively targets the ER, from where the protein can be relocated to peroxisomes on demand.
Single nucleus multi-omics links human cortical cell regulatory genome diversity to disease risk variants
Authors: Luo Chongyuan , Liu Hanqing , Xie Fangming , Armand Ethan J. , Siletti Kimberly , Bakken Trygve E. , Fang Rongxin , Doyle Wayne I. , Hodge Rebecca D. , Hu Lijuan , Wang Bang-An , Zhang Zhuzhu , Preissl Sebastian , Lee Dong-Sung , Zhou Jingtian , Niu Sheng-Yong , Castanon Rosa , Bartlett Anna , Rivkin Angeline , Wang Xinxin , Lucero Jacinta , Nery Joseph R. , Davis David A. , Mash Deborah C. , Dixon Jesse R. , Linnarsson Sten , Lein Ed , Behrens M. Margarita , Ren Bing , Mukamel Eran A. , Ecker Joseph R. 
Published: December 2019

ABSTRACTSingle-cell technologies enable measure of unique cellular signatures, but are typically limited to a single modality. Computational approaches allow integration of diverse single-cell datasets, but their efficacy is difficult to validate in the absence of authentic multi-omic measurements. To comprehensively assess the molecular phenotypes of single cells in tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmC2T-seq) and applied it to post-mortem human frontal cortex tissue. We developed a computational framework to validate fine-grained cell types using multi-modal information and assessed the effectiveness of computational integration methods. Correlation analysis in individual cells revealed distinct relations between methylation and gene expression. Our integrative approach enabled joint analyses of the methylome, transcriptome, chromatin accessibility and conformation for 63 human cortical cell types. We reconstructed regulatory lineages for cortical cell populations and found specific enrichment of genetic risk for neuropsychiatric traits, enabling prediction of cell types with causal roles in disease.
Modeling subcortical white matter stimulation
Authors: Dali Melissa , Goldman Jennifer S. , Pantz Olivier , Destexhe Alain , Mandonnet Emmanuel 
Published: December 2019

AbstractObjectiveIntracranial electrical stimulation of subcortical axonal tracts is particularly useful during brain surgery, where mapping helps identify and excise dysfunctional tissue while avoiding damage to functional structures. Stimulation parameters are generally set empirically and consequences for the spatial recruitment of axons within subcortical tracts are not well identified.ApproachComputational modeling is employed to study the effects of stimulation parameters on the recruitment of axons: monophasic versus biphasic stimuli induced with monopolar versus bipolar electrodes, oriented orthogonal or parallel to the tract, for isotropic and anisotropic tracts.Main resultsThe area and depth of axonal activation strongly depend on tissue conductivity and electrode parameters. The largest activation area results from biphasic stimulation with bipolar electrodes oriented orthogonal to axonal fasciculi, for anisotropic and especially isotropic tracts. For anisotropic tracts, the maximal activation depth is similar regardless of whether a monopolar or bipolar electrode is employed. For isotropic tracts, bipolar parallel and monopolar stimulation activate axons deeper than orthogonal bipolar stimulation. Attention is warranted during monophasic stimulation: a blockade of action potentials immediately under cathodes and a propagation of action potentials under anodes are found.SignificanceConsidering the spatial patterns of blockade and activation present during monophasic stimulation with both monopolar and bipolar electrodes, biphasic stimulation is recommended to explore subcortical axon responses during intraoperative mapping. Finally, the precise effect of electrical stimulation depends on conductivity profiles of tracts, and as such, should be explicitly considered for each individual subject and tract undergoing intracranial mapping.
Geochemical influences on nonenzymatic oligomerization of prebiotically relevant cyclic nucleotides
Authors: Dagar Shikha , Sarkar Susovan , Rajamani Sudha 
Published: December 2019

AbstractThe spontaneous emergence of RNA on the early Earth continues to remain an enigma in the field of origins of life. Few studies have looked at the nonenzymatic oligomerization of cyclic nucleotides under neutral to alkaline conditions, in fully dehydrated state. Herein, we systematically investigated the oligomerization of cyclic nucleotides under prebiotically relevant conditions, where starting reactants were subjected to repeated dehydration-rehydration (DH-RH) regimes, like they would have been on an early Earth. DH-RH conditions, a recurring geological theme, are driven by naturally occurring processes including diurnal cycles and tidal pool activity. These conditions have been shown to facilitate uphill oligomerization reactions in terrestrial geothermal niches, which are hypothesized to be pertinent sites for the emergence of life. 2′-3′ and 3′-5′ cyclic nucleotides of one purine-based (adenosine) and one pyrimidine-based (cytidine) system were evaluated in this study. Additionally, the effect of amphiphiles was also investigated. Furthermore, to discern the effect of ‘realistic’ conditions on this process, the reactions were also performed using hot spring water samples from an early Earth analogue environment. Our results showed that the oligomerization of cyclic nucleotides under DH-RH conditions resulted in intact informational oligomers. Amphiphiles increased the stability of, both, the starting monomers and the resultant oligomers. In analogue condition reactions, oligomerization of nucleotides and back-hydrolysis of the resultant oligomers was pronounced. Altogether, this study demonstrates how nonenzymatic oligomerization of cyclic purine and pyrimidine nucleotides, under laboratory-simulated and early Earth analogous conditions, could have resulted in RNA oligomers of a putative RNA World.
Interspecific hierarchies from aggressiveness and body size among the invasive alien hornet,Vespa velutina nigrithorax, and five native hornets in South Korea
Authors: Kwon Ohseok , Choi Moon Bo 
Published: December 2019

AbstractThe range of the invasive alien hornet,Vespa velutina nigrithorax, has been continuously expanding since its invasion of Korea in 2003. Here, we compared the aggressive behaviors and body size ofV. velutina nigrithoraxwith five native hornet species to identify the interspecific hierarchies that contributes to the spread of this species. Aggressive behaviors were classified into 11 categories and each interaction was scored as a win, loss, or tie. As a result,V. velutinawas superior toV. simillimain 153 fights whereV. velutinawon 71% and showed a high incidence of threatening behavior.V. mandariniaoutperformedV. velutinain 104 fights whereV. mandariniawon 91% and grappling behavior was common.V. analiswas superior toV. velutinain 67 fights whereV. analiswon 76% and showed a high amount of threatening behavior.V. crabrowas superior toV. velutinain 93 fights whereV. crabrowon 73% and showed a high rate of threatening behavior.V. dybowskiiwas superior toV. velutinain 132 fights whereV. dybowskiiwon 91%, and showed a high rate of threatening and grappling behaviors. The body size ofV. velutinawas larger thanV. simillima(although not statistically significant) and smaller than all otherVespaspecies. Therefore, according to the results of this study, the low interspecific hierarchies ofV. velutinaseems to be a major cause of slower spreading rates than it has shown in Europe. However, over time, its density has gradually increased within the forest, in which it seems to be overcoming its disadvantages and expanding its range, possibly as large colonies and good flying abilities make it easier to secure food.
Role of SHIP2 in cell repulsion regulated by Eph receptor and ephrin signaling
Authors: Ashlin Tim G. , Wu Zhonglin , Xu Qiling , Wilkinson David G. 
Published: December 2019

SUMMARYPrevious studies have found that activation of EphB2 and ephrinB1 that drives cell segregation leads to phosphorylation of the phosphoinositide phosphatase SHIP2 downstream of forward (EphB2) but not reverse (ephrinB1) signaling. We have analysed whether SHIP2 interacts with EphB2 and contributes to cell responses to EphB2-ephrinB1 signaling. We confirm that EphB2 activation leads to SHIP2 phosphorylation on Y1135 and find that they interact through the SH2 domain of SHIP2. There is thus a distinct mode of interaction from EphA2, which binds SHIP2 via its SAM domain. Knockdown of SHIP2 in EphB2 cells leads to decreased segregation from ephrinB1 cells, and a decrease in the repulsion response of EphB2 cells. SHIP2 knockdown in ephrinB1 cells also decreases their repulsion response, but does not disrupt segregation which is largely driven by forward signaling. These findings show that activation of EphB2 leads to recruitment and phosphorylation of SHIP2, and that SHIP2 contributes to cell repulsion responses that underlie cell segregation.
Strategies for value recovery from industrial waste: case studies of six industries from Brazil
Authors: Sellitto Miguel Afonso , Almeida Francieli Aparecida de 
Published: December 2019

Purpose
The purpose of this paper is to present possible strategic actions that aim to recover the value still remaining in industrial waste.

Design/methodology/approach
The research method is a multiple case study. The sample included six Brazilian companies of the footwear, metal-mechanics, pulp and paper, beverages, chemical and food industries. The study investigated the production process, waste generation, internal reuse, the destination of unused waste, difficulties and strategic challenges.

Findings
Possible strategies to recover the value remaining in industrial waste are increasing the internal reuse, developing new routes to other industries, reducing the waste generation, increasing the destination to cooperatives or recycling companies, which require studies to understand the legislation and agility in licensing and reducing the logistical cost of the destination.

Research limitations/implications
The study relies on six case studies. Further research shall encompass an entire industry, starting with hypotheses derived from the cases.

Practical implications
The main barriers observed for reuse and recycling are uncertainties and ambiguities in the interpretation of legislation, the difficulty for the environmental licensing for recycling operations, excessive logistics costs for exploration opportunities and the lack of research to reduce the waste generation and to increase the internal reuse.

Social implications
Waste managed by scavengers’ cooperatives can offer jobs to the people of vulnerable communities.

Originality/value
The study offers robust hypotheses to be tested in a survey on the capacity of a waste management strategy to create competitive advantage in the industry. The study establishes a relationship between waste management and three competitive enablers, compliance, corporate image and green market.
Enrolment status disparity: evidence from secondary education in Myanmar
Authors: Yoshida Natsuho 
Published: December 2019

Purpose
The purpose of this paper is to explore individual enrolment trajectories to fully understand the actual disparity in secondary education enrolment statuses among the different socio-economic status (SES) groups in a newly emerged nation, Myanmar.

Design/methodology/approach
The differences in enrolment statuses among various SES groups (high, middle and low) were examined based on enrolment trajectory diagrams and individual enrolment patterns using longitudinal data. The analyses utilised a sample of 932 students from government schools in the urban Yangon Region.

Findings
The results revealed that the ideal enrolment trajectory cases (i.e. entering secondary education at Myanmar’s official age and completing all grades without repetition) increased for the highest-SES level, whilst the cases with diverse and complex enrolment trajectories increased for the lower-SES levels. Additionally, over-aged students in the lowest-SES level (boys in particular) were more likely to demonstrate worse enrolment patterns.

Originality/value
By analysing disparities with enrolment trajectories rather than with the cross-sectional parity index, the findings offer clearer and more detailed evidence for the current enrolment status inequalities by SES level in Myanmar. This more complete evidence could allow for an effective accomplishment of worldwide equitable and universal secondary education.
An exploration of ecolabels and operating financial metrics
Authors: Hopkins Erin A. , Van Mullekom Jennifer H. 
Published: December 2019

PurposeAs the green economic bottom line is a strong motivating force when deciding to build, manage and/or operate green, this study aims to examine the financial impacts of green certifications on multifamily rental communities.Design/methodology/approachUsing a multiple regression methodology, operating financial variables are examined.FindingsMultifamily rental green buildings garner not only higher rental collections but also higher total expenses. When applying these higher rates to properties, the overall increase in rents outweighs the increases in total expenses.Originality/valueWhile multiple studies have focused on the office sector, this study begins to fill the literature gap within the multifamily rental sector regarding the economic impacts of green-certified buildings. The outcomes of this study have positive implications for the multifamily real estate industry by providing developers, owners, managers and related parties with a better understanding of the financial impacts of multifamily rental green buildings; however, more research is needed.
The influence of home-country institutions on servitization
Authors: Costa Hamilton Terni , Cahen Fernanda Ribeiro , Santos Juliana Bonomi 
Published: December 2019

Purpose
The purpose of this paper is to explore how home-country institutions influence firms’ servitization decisions. Existing studies have mostly neglected differences across countries and implicitly assumed the servitization process and drivers are homogenous across national institutional environments. The authors challenge this assumption.

Design/methodology/approach
Using case-based research, the authors explored the influence of formal institutions of the product, financial and labor markets on the servitization of two firms operating in a developed country and two in an emerging country.

Findings
The absence of robust home-country institutions did not necessarily hinder the servitization process. On the contrary, firms servitizate to overcome the difficulties posed by these institutional voids. The flexibility associated with service offerings enables firms to create viable alternatives to cope with taxes, lack of infrastructure and qualified labor force.

Originality/value
These outcomes contribute to the servitization literature, which has mainly focused on single-country studies and takes for granted the institutional differences between countries. The findings suggest future studies need to consider how and, to what extent, the country where the company is located influences servitization strategies and processes. Such reflections will improve the inferences made concerning firms’ servitization. For practitioners, the results suggest that the move into the provision of services can be a fruitful strategy to overcome the difficulties faced in emerging markets.
e-Business management assessment: framework proposal through case study analysis
Authors: Isaías Pedro , Carvalho Luisa Cagica , Cassundé Junior Nildo , Cassundé Fernanda Roda 
Published: December 2019

Purpose
The purpose of this paper is to propose an e-business assessment framework for organizations that aim to enhance the effectiveness of their online presence and maximize the benefits that result from it. The framework is based on three main pillars derived from the academic literature research: e-marketing strategies, customer relationship management (CRM) strategies and business model strategies.

Design/methodology/approach
This paper reviews the literature from e-Marketing, CRM and business model strategies, leading to the generation of an e-Business assessment framework. Second, it takes 19 case studies and analyzes them using ATLAS.ti, through qualitative content analysis, to validate that framework.

Findings
Pragmatic advice for practitioners derives from research results considering that this framework enables managers to characterize the company in terms of its e-business approach, making it possible to determine the level of depth of competitive online strategies. Lessons for an improved e-business approach can be derived from this paper.

Originality/value
This study proposes a novel e-business framework to assist organizations that want to have an online presence. This framework is comprised of the factors identified in the literature review that contribute to define and scope that online presence. The framework is then validated through the collection of 19 case studies of companies that have this online presence, validating the theoretical findings.
Islamic branding: insights from a conceptual perspective
Authors: Bukhari Syeda Nazish Zahra , Isa Salmi Mohd 
Published: December 2019

Purpose
The purpose of this study is to propose a conceptual model of Islamic branding. Based on the theory of self-congruity and existing literature, the conceptual model proposes three antecedents that can form the building blocks of Islamic branding.

Design/methodology/approach
The authors have developed a conceptual model to propose the antecedents of the Islamic branding construct based on the theory of self-congruity. The antecedents are adapted from existing literature and customized according to the Muslim consumer market. Three hypotheses are formulated on the basis of the proposed model and justified from existing literature.

Findings
The proposed Islamic branding model can be applied to both local and multinational brands in both Muslim majority and minority markets. Religiosity, Islamic brand knowledge and Islamic corporate social responsibility are proposed as the antecedents of Islamic branding. Muslim consumers are attracted to brands that portray congruity with their religious values. The proposed antecedents of Islamic branding can result in the subsequent formation of an emotional attachment between the Muslim consumer and the respective Islamic brand, and thereby a stronger Islamic brand.

Research limitations/implications
The proposed Islamic branding model has not been empirically tested in this study.

Originality/value
Islamic branding is in the infancy stage of conceptual development. Currently, limited research exists on the operationalization of this construct. A gap exists in the literature regarding models and instruments for the operationalization and development of Islamic branding. The proposed model attempts to fill the conceptual gaps while taking into account the heterogeneity of the Muslim consumer market. Up until now, religiosity, Islamic brand knowledge and corporate social responsibility have not been studied as antecedents of Islamic branding. This study offers new insights by proposing customized brand-building blocks for an organization’s Islamic branding strategy based on theoretical grounds.