bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced InhibitionIn vitro
Authors: Latchoumane Charles-Francois V. , Jackson LaDonya , Eslampanah Sendi Mohammad .S , Tehrani Kayvan F. , Mortensen Luke J. , Stice Steven L. , Ghovanloo Maysam , Karumbaiah Lohitash 
Published: June 2018

ABSTRACTFunctional electrical stimulation (FES) is rapidly gaining traction as a therapeutic tool for mediating the repair and recovery of the injured central nervous system (CNS). However, the underlying mechanisms and impact of these stimulation paradigms at a molecular, cellular and network level remain largely unknown. In this study, we used embryonic stem cell (ESC)-derived neuron and glial cocultures to investigate network maturation following acute administration of L-glutamate, which is a known mediator of excitotoxicity following CNS injury. We then modulated network maturation using chronic low frequency stimulation (LFS) and direct current stimulation (DCS) protocols. We demonstrated that L-glutamate impaired the rate of maturation of ESC-derived neurons and glia immediately and over a week following acute treatment. The administration of chronic LFS and DCS protocols individually following L-glutamate infusion significantly promoted the excitability of neurons as well as network synchrony, while the combination of LFS/DCS did not. qRT-PCR analysis revealed that LFS and DCS alone significantly up-regulated the expression of excitability and plasticity-related transcripts encoding N-methyl-D-aspartate (NMDA) receptor subunit (NR2A), brain-derived neurotrophic factor (BDNF) and Ras-related protein (RAB3A). In contrast, the simultaneous administration of LFS/DCS down-regulatedBDNFandRAB3Aexpression. Our results demonstrate that LFS and DCS stimulation can modulate network maturation excitability and synchrony following the acute administration of an inhibitory dose of L-glutamate, as well as an upregulation of NR2A, BDNF and RAB3A gene expression. Our study also provides a novel framework for investigating the effects of electrical stimulation on neuronal responses and network formation/repair after traumatic brain injury.
A Drosophila CRISPR/Cas9 toolkit for conditionally manipulating gene expression in the prothoracic gland as a test case for polytene tissues
Authors: Huynh Nhan , King-Jones Kirst 
Published: June 2018

AbstractTargeting gene function with spatial or temporal specificity is a key goal in molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some standard approaches are problematic. For instance, simple tissue-specific or global overexpression of Cas9 can cause significant lethality or developmental delays even in the absence of gRNAs. In particular, we found that Gal4-mediated expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a suitable strategy to disrupt gene expression, since Cas9 alone caused widespread lethality. The PG gland is widely used for studying endocrine gland function during animal development, but tools validating PG-specific RNAi phenotypes are lacking. Here, we present a collection of modular gateway-compatible CRISPR-Cas9 tools that allow precise modulation of target gene activity with temporal and spatial specificity. We also demonstrate that Cas9 fused to the progesterone ligand-binding domain can be used to activate gene expression via RU486. Using these approaches, we were able to avoid the lethality associated with simple GAL4-mediated overexpression of Cas9 in the PG. Given that the PG is a polytene tissue, we conclude that these tools work effectively in endoreplicating cells where Cas9 has to target multiple copies of the same locus. Our toolkit can be easily adapted for other tissues and can be used both for gain-and loss-of-function studies.
Insights on protein thermal stability: a graph representation of molecular interactions
Authors: Miotto Mattia , Olimpieri Pier Paolo , Rienzo Lorenzo Di , Ambrosetti Francesco , Corsi Pietro , Lepore Rosalba , Tartaglia Gian Gaetano , Milanetti Edoardo 
Published: June 2018

ABSTRACTUnderstanding the molecular mechanisms of thermal stability is a challenge in protein biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, which are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity.Here, we present a novel graph-theoretical framework to assess thermal stability based on the structure without any aprioriinformation. In our approach we describe proteins as energy-weighted graphs and compare them using ensembles of interaction networks. Investigating the position of specific interactions within the 3D native structure, we developed a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and Area Under the Roc Curve of 78%.
An automated, high-throughput method for standardizing image color profiles to improve image-based plant phenotyping
Authors: Berry Jeffrey C. , Fahlgren Noah , Pokorny Alexandria A. , Bart Rebecca , Veley Kira M. 
Published: June 2018

ABSTRACTHigh-throughput phenotyping has emerged as a powerful method for studying plant biology. Large image-based datasets are generated and analyzed with automated image analysis pipelines. A major challenge associated with these analyses is variation in image quality that can inadvertently bias results. Images are made up of tuples of data called pixels, which consist of R, G, and B values, arranged in a grid. Many factors, for example image brightness, can influence the quality of the image that is captured. These factors alter the values of the pixels within images and consequently can bias the data and downstream analyses. Here, we provide an automated method to adjust an image-based dataset so that brightness, contrast, and color profile is standardized. The correction method is a collection of linear models that adjusts pixel tuples based on a reference panel of colors. We apply this technique to a set of images taken in a high-throughput imaging facility and successfully detect variance within the image dataset. In this case, variation resulted from temperature-dependent light intensity throughout the experiment. Using this correction method, we were able to standardize images throughout the dataset, and we show that this correction enhanced our ability to accurately quantify morphological measurements within each image. We implement this technique in a high-throughput pipeline available with this paper, and it is also implemented in PlantCV.
Chemically Accurate Relative Folding Stability of RNA Hairpins from Molecular Simulations
Authors: Smith Louis G. , Tan Zhen , Spasic Aleksandar , Dutta Debapratim , Salas-Estrada Leslie A. , Grossfield Alan , Mathews David H. 
Published: June 2018

AbstractThis study describes a comparison between melts and simulated stabilities of the same RNAs that could be used to benchmark RNA force fields, and potentially to determine future melt-ing experiments. Using umbrella sampling molecular simulations of three 12-nucleotide RNA hairpin stem loops, for which there are experimentally determined free energies of unfold-ing, we projected unfolding onto the reaction coordinate of end to end (5′ to 3′ hydroxyl oxygen) distance. We estimate the free energy change of the transition from the native con-formation to a fully extended conformation—the stretched state—with no hydrogen bonds between non-neighboring bases. Each simulation was performed four times using the AM-BER FF99+bsc0+χOL3 force field and each window, spaced at 1 Å intervals, was sampled for 1 μs, for a total of 552 μs of simulation. We compared differences in the simulated free energy changes to analogous differences in free energies from optical melting experiments using ther-modynamic cycles where the free energy change between stretched and random coil sequences is assumed to be sequence independent. The differences between experimental and simulated ΔΔG° are on average 1.00 ± 0.66 kcal/mol, which is chemically accurate and suggests analo-gous simulations could be used predictively. We also report a novel method to identify where replica free energies diverge along the reaction coordinate, thus indicating where additional sampling would most improve convergence. We conclude by discussing methods to more economically perform such simulations.
Dual RNAseq of human leprosy lesions identifies bacterial determinants linked to host immune response
Authors: Montoya Dennis , Andrade Priscila R. , Silva Bruno J. A. , Teles Rosane M. B. , Bryson Bryan , Sadanand Saheli , Noel Teia , Lu Jing , Sarno Euzenir , Arnvig Kristine B. , Young Douglas , Lahiri Ramanuj , Williams Diana L. , Fortune Sarah , Bloom Barry R. , Pellegrini Matteo , Modlin Robert L. 
Published: June 2018

SummaryTo understand how the interaction between an intracellular bacterium and the host immune system contributes to outcome at the site of infection, we studied leprosy, a disease that forms a clinical spectrum, in which progressive infection by the intracellular bacterium Mycobacterium leprae is characterized by the production of type | IFNs and antibody production. We performed dual RNAseq on patient lesions, identifying a continuum of distinct bacterial states that are linked to the host immune response. The bacterial burden, represented by the fraction of bacterial transcripts, correlates with a host type | IFN gene signature, known to inhibit antimicrobial responses. Second, the bacterial transcriptional activity, defined by the bacterial mRNA/rRNA ratio, links bacterial heat shock proteins with the BAFF-BCMA host antibody response pathway. Our findings provide a platform for interrogation of host and pathogen transcriptomes at the site of infection, allowing insight into mechanisms of inflammation in human disease.
5′ Modifications Improve Potency and Efficacy of DNA Donors for Precision Genome Editing
Authors: Ghanta Krishna S , Chen Zexiang , Mir Aamir , Dokshin Gregoriy A , Krishnamurthy Pranathi M , Yoon Yeonsoo , Gallant Judith , Xu Ping , Zhang Xiao-Ou , Ozturk Ahmet , Shin Masahiro , Idrizi Feston , Liu Pengpeng , Gneid Hassan , Lawson Nathan D , Rivera-Pérez Jaime A , Sontheimer Erik J , Watts Jonathan K , Mello Craig C 
Published: June 2018

AbstractNuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an exogenously supplied DNA repair template (donor) directly into a targeted genomic location. Unfortunately, particularly for long insertions, toxicity and delivery considerations associated with repair template DNA can limit HDR efficacy. Here, we explore chemical modifications to both double-stranded and single-stranded DNA-repair templates. We describe 5′-terminal modifications, including in its simplest form the incorporation of triethylene glycol (TEG) moieties, that consistently increase the frequency of precision editing in the germlines of three animal models (Caenorhabditis elegans, zebrafish, mice) and in cultured human cells.
Brr2 is a splicing fidelity factor
Authors: Mayerle Megan , Guthrie Christine 
Published: June 2018

AbstractMany spliceosomal DExD/H box helicases act as fidelity factors during pre-mRNA splicing, promoting on-pathway interactions while simultaneously minimizing errors. Mutations linked to Retinitis Pigmentosa (RP), a form of heritable blindness, map to key domains of spliceosomal helicase Brr2 (SNRNP200in humans). Previous data show that such mutations negatively impact spliceosome activation, likely due to defects inbrr2-RPRNA binding, helicase, and ATPase activities. Furthermore, data from human reporter constructs suggest thatbrr2-RPmight impact 5′ splice site selection. Here we undertake a systematic analysis ofbrr2-RPeffects on splicing fidelity. We show that a subset ofbrr2-RPmutants exhibit intron retentionin vivo. Furthermore,brr2-RPmutants display hyperaccurate and/or error-prone splicing of a variety of splicing reporters. Branch-site fidelity is particularly impacted in this reporter assay. In addition, multiplebrr2-RPalleles genetically interact withprp16alleles known to impact the fidelity of branch site selection. Together these data implicate Brr2 in the fidelity of branch-site selection, and suggest that RP results not just from defects in spliceosome activation, but also from fidelity defects arising throughout the splicing cycle and in splicing fidelity.
Can I have it all? Emerging adult women’s positions on balancing career and family
Authors: Ezzedeen Souha R. , Budworth Marie-Hélène , Baker Susan D. 
Published: June 2018

Purpose
Emerging adult women are actively engaged in career and family explorations, amidst changing opportunities and constraints. The purpose of this paper is to investigate whether such women felt they could balance a high-achieving career and a family life, or what has become known in the popular discourse as women “having it all.”

Design/methodology/approach
This qualitative study utilized focus groups to explore subjective perceptions of balancing career and family held by emerging adult women. The sample (n=69) comprised female university students in a large Canadian metropolitan area.

Findings
Thematic analyses unearthed six distinct yet overlapping positions on the possibility of balancing career and family: Optimism (“I can have it all.”), Pessimism (“I cannot have it all.”), Uncertainty (“I am not sure I can have it all.”), Choice (“I don’t want to have it all.”), Pragmatism (“This is what I need to do to have it all.”) and Support (“Will I access the support necessary to have it all?”).

Research limitations/implications
Limitations include the potential of focus groups to elicit group polarization and to lead participants to censor opinions to conform to conversations. Still, the study reveals more nuanced positions held by women than reported earlier.

Originality/value
The study extends prior research by revealing the range of positions held by women toward career and family, highlighting women’s understanding of the complex issues involved and showcasing their awareness of the crucial role of social support.
ABBYY: the digitization of language and text
Authors: Shapenko Andrey , Korovkin Vladimir , Leleux Benoit 
Published: June 2018

Subject area
Entrepreneurship, Innovation Management, Bringing Technology to Market, International Growth Strategy from Emerging Markets, Russia, B2B Marketing.

Study level/applicability
MBA and executive education programs, technology management programs and electives.

Case overview
The case investigates the 20-years growth story of ABBYY, one of the most successful Russian technological companies in a global market. It covers the company’s roots, development of unique technology, evolution of products, market development and globalization and discusses a strategic threat from Google Translate to the company’s sustainable position and its business model.

Expected learning outcomes
The expected learning outcome is to discuss the key issues associated with establishing, growing and globalizing technology-driven business in an emerging market: bringing technology to market, defining customer value proposition, entering overseas markets from Russia, building partnerships, developing organizational structure to fit growth, financing rapid growth and solving “Innovator’s Dilemma”.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 3: Entrepreneurship.
Analyzing Iran’s science and technology foresight programs: recommendations for further practices
Authors: Hafezi Reza , Malekifar Siavosh , Akhavan Amirnaser 
Published: June 2018

Purpose
Studying previous science and technology (S&T) foresight activities reveals information that helps decision makers to redesign policy-making templates aimed at dealing with new millennium challenges. To propose policy recommendations about further S&T foresight programs in Iran, this paper aims to propose a three-phase process to study historical S&T foresight activities at national and sub-national level since 2005 to 2015, to analyze the state of selected activities to discover weaknesses and potential solutions and, finally, to provide strategies and tactics to improve further S&T foresight activities through an expert-based process.

Design/methodology/approach
This paper provides a three-stage methodology, designed to survey Iranian historical foresight practices (study) using scoping framework equipped with additional features, diagnosis and evaluating (analyze) and finally proposing recommendations to organize and implement more efficient further foresight practices (design) to initialize further practices in developing countries such as Iran.

Findings
Although concerns about future and the importance of foresight activities are raised however Iranian foresight community needs to be developed. As noted in Section 5, Iranian foresight facilitators and specialist are biased to limited methodologies and methods; therefore, creating foresight networks and developing communities is strongly recommended.

Research limitations/implications
The main constraint of this research was lack of valid data in the case of some Iranian S&T foresight programs.

Originality/value
Iran as a developing country needs to plan for long-run programs; however, there is no integrated study which reviews and analyzes the previous attempts to dedicate insights about how to reframe existing foresight paradigms. As foresight practices facilitate the paths toward sustainability, analyzing and diagnosis of a series of foresight practices in a devolving country may initialize designing such efforts in less developed world.
Bank selection criteria and satisfaction of retail customers of Islamic banks in Bangladesh
Authors: Iqbal Mehree , Nisha Nabila , Rashid Mamunur 
Published: June 2018

Purpose
The purpose of this paper is to argue that “being Islamic” is already embedded in the decision frame of the Muslim consumers when choosing their Islamic banks, and hence, the bank selection criteria of these Muslim consumers will be dominated by non-faith-based factors.

Design/methodology/approach
This study took the context of retail consumers of Islamic banks of Bangladesh—the fourth largest Muslim populated country in the world, having great potential of developing an Islamic ecosystem. The study employed survey method using structured questionnaire on 311 respondents from 35 branches of six Islamic banks in Dhaka—the capital city of Bangladesh. Exploratory factor analysis, followed by multivariate regression analysis, was conducted to identify the determinants of satisfaction among Muslim retail bank customers.

Findings
The study forwards three important findings. First, faith-based bank selection criterion (i.e. Islam) is not a stand-alone factor anymore; rather, the items of this factor are embedded into other non-faith-based factors. Second, among the non-faith-based factors, commitment of the bank, competence and compassion of the bank employees have topped the list of bank selection criteria. Third, competence, commitment and corporate image of the bank had relatively more influence on satisfaction when compared to compassion and convenience.

Practical implications
Since Shari’ah compliance is already embedded in Islamic banking system, Islamic bankers should now focus on strategic targeting of their customers based on non-faith-based operational determinants.

Originality/value
This study presents that non-faith-based selection criteria are more influential in Islamic bank selection decision.
Inter-organizational relationships with core and peripheral partners in heritage tourism clusters
Authors: Elche Dioni , García-Villaverde Pedro M. , Martínez-Pérez Ángela 
Published: June 2018

PurposeThis paper aims to analyze the effects of inter-organizational relationships with core and peripheral partners on innovation in heritage tourism clusters.Design/methodology/approachThe empirical analysis uses original data (collected by means of a postal questionnaire) based at UNESCO World Heritage Cities in Spain. The sample consists of 215 companies, and the methodology used is hierarchical linear regression.FindingsThe authors identify divergent effects of relationships with core and peripheral partners on innovation. In particular, the effect of core partners has an inverted U-shaped form, while that of peripheral partners is U-shaped.Research limitations/implicationsThe results may be extrapolated to other heritage tourism clusters located in World Heritage Cities with some precaution. The paper does not jointly analyze the effects of relationships with core and peripheral partners on the innovation of firms in tourism clusters.Practical/implicationsClustered tourism firms should not rely only on relationships with core agents, because beyond a critical threshold, returns in terms of innovation diminish. Firms should strive to establish relationships with peripheral agents in spite of the initial difficulties and the costs associated with network building, because positive returns soon materialize.Originality/valueThis paper contributes to the literature on inter-organizational relationships by analyzing the impact of relationships with core and peripheral partners on innovation in clustered firms. The authors highlight the existence of the divergent curvilinear effects of these relationships on heritage tourism clusters.
The dynamics of inflation, exchange rates and the trade balance in a small economy
Authors: Yiheyis Zelealem , Musila Jacob 
Published: June 2018

PurposeThe purpose of this study is to examine the temporal relationships between inflation and exchange rate changes and their implications for the trade balance in Uganda, which saw persistent trade deficits, rising inflation and disinflation episodes, as well as significant exchange-rate realignments and other liberalization measures over the sample period considered.Design/methodology/approachThe short-run dynamics of the variables in question and the pattern of their long-run relationships are examined applying the bounds testing approach to cointegration on quarterly data.FindingsThe estimates suggest that, in the long run, a real depreciation leads to an increase in inflation; and that both real depreciation and inflation exert no significant effect on the trade balance. The estimated short-run dynamics suggest a causal relationship between the trade balance and the real exchange rate and between the real exchange rate and inflation, which is also found responsive to developments in the foreign sector. Taken together, the short-run and long-run multipliers seem to provide a weak support for the J-curve effect, while no evidence is found for the presence of the S-curve effect.Originality/valueThe study sheds light on the relationship among real exchange rate, inflation and the trade balance in the context of a small developing economy; it highlights that an improvement in the trade balance requires more than an appropriate exchange rate policy and underscores the importance of other policies in strengthening the external sector of the economy.