bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-to-cell expression dispersion of B-cell surface proteins displays genetic variation among humans
Authors: Triqueneaux Gérard , Burny Claire , Symmons Orsolya , Janczarski Stéphane , Gruffat Henri , Yvert Gaël 
Published: October 2019

ABSTRACTVariability in gene expression across a population of homogeneous cells is known to influence various biological processes. In model organisms, natural genetic variants were found that modify expressiondispersion(variability at a fixed mean) but whether such effects exist in humans has not been fully demonstrated. Here, we analyzed single-cell expression of four proteins (CD23, CD55, CD63 and CD86) across cell lines derived from individuals of the Yoruba population. Using data from over 30 million cells, we found substantial inter-individual variation of dispersion. We demonstrate, viade novocell line generation and subcloning experiments, that this variation exceeds the variation associated with cellular immortalization. By association mapping, we linked the expression dispersion of CD63 to thers971SNP. Our results show that human DNA variants can have inherently-probabilistic effects on gene expression. Such subtle genetic effects may participate to phenotypic variation and disease predisposition.
PRMT5 in T helper lymphocytes is essential for cholesterol biosynthesis-mediated Th17 responses and autoimmunity
Authors: Webb Lindsay M. , Sengupta Shouvonik , Edell Claudia , Amici Stephanie A. , Narvaez-Miranda Janiret , Kennemer Austin , Guerau-de-Arellano Mireia 
Published: October 2019

AbstractProtein Arginine Methyltransferase (PRMT) 5 catalyzes symmetric dimethylation of arginine, a post-translational modification involved in cancer and embryonic development. However, the role of PRMT5 in T helper (Th) cell polarization and Th cell-mediated disease has not yet been elucidated. Here we report that PRMT5 is necessary for Th17 differentiation and EAE, via enhancement of cholesterol biosynthesis and activation of ROR-γt. PRMT5 additionally controls thymic and peripheral homeostasis in the CD4 Th cell life cycle, as well as iNK T and CD8 T cell development or maintenance, respectively. Overall, our two conditional PRMT5 KO models that selectively delete PRMT5 in all T cells (T-PRMT5Δ/Δ) or Th cells (iCD4-PRMT5Δ/Δ) unveil a crucial role for PRMT5 in T cell proliferation, Th17 responses and disease. These results point to Th PRMT5 and its downstream cholesterol biosynthesis pathway as promising therapeutic targets in Th17-mediated diseases.
Daughterless, theDrosophilaorthologue of TCF4, is required for associative learning and maintenance of synaptic proteome
Authors: Tamberg Laura , Jaago Mariliis , Säälik Kristi , Shubina Anastassia , Kiir Carl Sander , Sirp Alex , Timmusk Tõnis , Palgi Mari 
Published: October 2019

AbstractMammalian Transcription Factor 4 (TCF4) has been linked to schizophrenia and intellectual disabilities like Pitt-Hopkins syndrome (PTHS). Here we show that similarly to mammalian TCF4, fruit fly orthologue Daughterless (Da) is expressed in theDrosophilabrain structures associated with learning and memory, the mushroom bodies. Furthermore, silencing ofdain mushroom body neurons impairs appetitive associative learning of the larvae and leads to decreased levels of the synaptic proteins Synapsin (Syn) and discs large 1 (dlg1) suggesting the involvement of Da in memory formation. Here we demonstrate thatSynanddlg1are direct target genes of Da in adultDrosophilaheads, since Da binds to the regulatory regions of these genes and the modulation of Da levels alter the levels ofSynanddlg1mRNA. Silencing ofdaalso affects negative geotaxis of the adult flies suggesting the impairment of locomotor function. Overall, our findings suggest that Da regulatesDrosophilalarval memory and adult negative geotaxis possibly via its synaptic target genesSynanddlg1. These behavioural phenotypes can be further used as a PTHS model to screen for therapeutics.Summary statementHuman TCF4, a bHLH transcription factor, is associated with intellectual disability and schizophrenia. Here we propose aDrosophilamodel for human disease studies using TCF4 orthologue in fruit fly, Daughterless.
A vast resource of allelic expression data spanning human tissues
Authors: Castel Stephane E. , Aguet François , Mohammadi Pejman ,   GTEx Consortium, Ardlie Kristin G. , Lappalainen Tuuli 
Published: October 2019

AbstractAllele specific expression (ASE) analysis robustly measurescisregulatory effects. Here, we present a vast ASE resource generated from the GTEx v8 release, containing 15,253 samples spanning 54 human tissues for a total of 431 million measurements of ASE at the SNP-level and 153 million measurements at the haplotype-level. In addition, we developed an extension of our tool phASER that allows effect sizes ofcisregulatory variants to be estimated using haplotype-level ASE data. This ASE resource is the largest to date and we are able to make haplotype-level data publicly available. We anticipate that the availability of this resource will enable future studies of regulatory variation across human tissues.
Contribution of unfixed transposable element insertions to human regulatory variation
Authors: Goubert Clément , Zevallos Nicolas Arce , Feschotte Cédric 
Published: October 2019

AbstractThousands of unfixed transposable element (TE) insertions segregate in the human population, but little is known about their impact on genome function. Recently, a few studies associated polymorphic TE insertions to mRNA levels of adjacent genes, but the biological significance of these associations, their replicability across cell types, and the mechanisms by which they may regulate genes remain largely unknown. Here we performed a TE-expression QTL analysis of 444 lymphoblastoid cell lines and 294 induced pluripotent stem cells using a newly developed set of genotypes for 2,806 polymorphic TE insertions. We identified 211 and 324 TE-eQTL acting in cis in each respective cell type. Approximately one fourth were shared across cell types with strongly correlated effects. Furthermore, analysis of chromatin accessibility QTL in a subset of the lymphoblastoid cell lines suggests that unfixed TEs often modulate the activity of enhancers and other distal regulatory DNA elements, which tend to lose accessibility when a TE inserts within them. We also document a case of an unfixed TE likely influencing gene expression at the post-transcriptional level. Our study points to broad and diverse cis-regulatory effects of unfixed TEs in the human population and underscores their plausible contribution to phenotypic variation.
Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor
Authors: Jenni Simon , Bloyet Louis-Marie , Diaz-Avalos Ruben , Liang Bo , Whelan Sean P. J. , Grigorieff Nikolaus , Harrison Stephen C. 
Published: October 2019

SUMMARYThe large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated and polyadenylated mRNAs and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 Å resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with the RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5’-nucleotide.
Template switching by a group II intron reverse transcriptase: biochemical analysis and implications for RNA-seq
Authors: Lentzsch Alfred M. , Yao Jun , Russell Rick , Lambowitz Alan M. 
Published: October 2019

ABSTRACTThe reverse transcriptases (RTs) encoded by mobile group II intron and other non-LTR-retro-elements differ from retroviral RTs in being able to template switch from the 5’ end of one template to the 3’ end of another without pre-existing complementarity between the donor and acceptor nucleic acids. Here, we used the ability of a thermostable group II intron RT (TGIRT; GsI-IIC RT) to template switch directly from synthetic RNA template/DNA primer duplexes having either a blunt end or a 3’-DNA overhang end to establish a complete kinetic framework for the reaction and identify conditions that more efficiently capture acceptor RNAs or DNAs. The rate and amplitude of template switching are optimal from starter duplexes with a single nucleotide 3’-DNA overhang complementary to the 3’ nucleotide of the acceptor RNA, suggesting a role for non-templated nucleotide addition of a complementary nucleotide to the 3’ end of cDNAs synthesized from natural templates. Longer 3’-DNA overhangs progressively decrease the rate of template switching, even when complementary to the 3’ end of the acceptor template. The reliance on a single base pair with the 3’ nucleotide of the acceptor together with discrimination against mismatches and the high processivity of the enzyme enable synthesis of full-length DNA copies of nucleic acids beginning directly at their 3’ end. We discuss possible biological functions of the template-switching activity of group II intron and other non-LTR-retroelements RTs, as well as the optimization of this activity for adapter addition in RNA-and DNA-seq.
Generation of “nanometer-size aggregates” using Solubility Controlling Peptide tags and their ability to increase a protein’s immunogenicity in vivo
Authors: Rahman Nafsoon , Islam Mohammad Monirul , Unzai Satoru , Miura Shiho , Kuroda Yutaka 
Published: October 2019

AbstractSub-visible aggregates of proteins are suspected to cause adverse immune response, and a recent FDA guideline has recommended the monitoring of micrometer-size aggregates (2-10 μm) though recognizing that the underlying mechanism behind aggregation and immunogenicity remains unclear. Here, we report a correlation between the immunogenicity and the size of nanometer-scale aggregates of a small 6.5 kDa model protein, Bovine Pancreatic Trypsin Inhibitor (BPTI) variant. BPTI-19A, a monomeric and non-immunogenic protein, was oligomerized into sub-visible aggregates with hydrodynamic radii (Rh) of 3~4 nm by attaching hydrophobic solubility controlling peptide (SCP) tags to its C-terminus. The results showed that the association of non-immunogenic BPTI into nanometer-size aggregates made it highly immunogenic, as assessed by the IgG antibody titers of the mice’s sera. Overall, the study emphasizes that sub-visible aggregates, as small as a few nanometers, which are presently ignored, are worth monitoring for deciphering the origin of undesired immunogenicity of therapeutic proteins.
Flexible Fitting of Biomolecular Structures to Atomic Force Microscopy Images via Biased Molecular Simulations
Authors: Niina Toru , Fuchigami Sotaro , Takada Shoji 
Published: October 2019

AbstractAtomic force microscopy (AFM) is a prominent imaging technology that observes large-scale structural dynamics of biomolecules near the physiological condition, but the AFM data are limited to the surface shape of specimens. Rigid-body fitting methods were developed to obtain molecular structures that fit to an AFM image, without accounting for conformational changes. Here we developed a method to fit flexibly a three-dimensional biomolecular structure into an AFM image. First, we describe a method to produce a pseudo-AFM image from a given three-dimensional structure in a differentiable form. Then, using a correlation function between the experimental AFM image and the computational pseudo-AFM image, we developed a flexible fitting molecular dynamics (MD) simulation method, by which we obtain protein structures that well fit to the given AFM image. We first test it with a twin-experiment; for a synthetic AFM image produced from a protein structure different from its native conformation, the flexible fitting MD simulations sampled those that fit well the AFM image. Then, parameter dependence in the protocol is discussed. Finally, we applied the method to a real experimental AFM image for a flagellar protein FlhA, demonstrating its applicability. We also test the rigid-body fitting of a fixed structure to the AFM image. Our method will be a general tool for structure modeling based on AFM images and is publicly available through CafeMol software.
An investigational analysis on forecasting intraday values
Authors: Manickavasagam Jeevananthan , S. Visalakshmi 
Published: October 2019

Purpose
The algorithmic trading has advanced exponentially and necessitates the evaluation of intraday stock market forecasting on the grounds that any stock market series are foreseen to follow the random walk hypothesis. The purpose of this paper is to forecast the intraday values of stock indices using data mining techniques and compare the techniques’ performance in different markets to accomplish the best results.

Design/methodology/approach
This study investigates the intraday values (every 60th-minute closing value) of four different markets (namely, UK, Australia, India and China) spanning from April 1, 2017 to March 31, 2018. The forecasting performance of multivariate adaptive regression spline (MARSplines), support vector regression (SVR), backpropagation neural network (BPNN) and autoregression (1) are compared using statistical measures. Robustness evaluation is done to check the performance of the models on the relative ratios of the data.

Findings
MARSplines produces better results than the compared models in forecasting every 60th minute of selected stocks and stock indices. Next to MARSplines, SVR outperforms neural network and autoregression (1) models. The MARSplines proved to be more robust than the other models.

Practical implications
Forecasting provides a substantial benchmark for companies, which entails long-run operations. Significant profit can be earned by successfully predicting the stock’s future price. The traders have to outperform the market using techniques. Policy makers need to estimate the future prices/trends in the stock market to identify the link between the financial instruments and monetary policy which gives higher insights about the mechanism of existing policy and to know the role of financial assets in many channels. Thus, this study expects that the proposed model can create significant profits for traders by more precisely forecasting the stock market.

Originality/value
This study contributes to the high-frequency forecasting literature using MARSplines, SVR and BPNN. Finding the most effective way of forecasting the stock market is imperative for traders and portfolio managers for investment decisions. This study reveals the changing levels of trends in investing and expectation of significant gains in a short time through intraday trading.
The current state of brand management research
Authors: Shtovba Serhiy , Shtovba Olena , Filatova Lyubov 
Published: October 2019

Purpose
The purpose of this paper is to identify leaders and trends in branding research studies, undertaken during 2000-2019. Identification was made in the following categories: most popular subjects; most productive countries; most productive institutions; most productive scholars; most productive sources; most cited publications and most cited scholars.

Design/methodology/approach
Bibliometric analysis based on data from Scopus and Dimensions.

Findings
The majority of branding publications belong to business and management. The interest toward this research field, however, declines mostly in favor of cultural studies, psychology, sociology, etc. The majority of publications on branding are concentrated in the USA, UK and Australia. Griffith University has become a leader in the number of branding publications within 2000-2019. T C Melewar is a leader by the number of branding publications among scholars. Journal of Brand Management has been a leader among sources. Journal of Marketing is a leader by the number of the most cited papers.

Research limitations/implications
The authors analyze the automatically formed results on search query without human meddling.

Originality/value
For the first time, bibliometric analysis was carried out simultaneously upon the two bases – Scopus and Dimensions.
Challenges to economic integration and social inclusion of Syrian refugees in Turkey
Authors: Bache Christina 
Published: October 2019

Purpose
The following question drove this research: Would the pursuit of a rights-based approach, one that considers local dynamics and political sensitivities result in greater economic integration and social inclusion of Syrian refugees in Turkey? The paper aims to discuss this issue.

Design/methodology/approach
This piece draws on independent research the author conducted in Turkey and other frontline states to the war in Syria from 2016 to 2018.

Findings
Despite a shift in government policy toward Syrian refugees, without an overarching rights-based approach that includes the participation of all stakeholders and considers local dynamics and political sensitivities, enhancing the livelihood security of Syrian refugees and vulnerable members of host communities remains bleak in Turkey.

Originality/value
This original paper closely examines the Government of Turkey’s response to the humanitarian crisis that was precipitated by the armed conflict in Syria. The paper also examines the socioeconomic dynamics and increased tensions between the Syrian refugee and host communities.
Commentary: considering the social value of IB
Authors: Doh Jonathan 
Published: October 2019

Purpose
In this viewpoint, the author critically aims to examine the papers by Sinkovics and Archie-Acheampong (2019, this issue) “The social value creation of MNEs – a literature review across multiple academic fields” and by Rygh (2019, this issue) “Social value creation by multinational enterprises: the next “big question” for international business research?” and offer an appraisal of the papers’ merits as well as thoughts for further development of research on social value creation, critical international business and work that can conceivably contribute to scholarship on global grand challenges.

Design/methodology/approach
The author’s approach is a reflexive review of two papers in the Critical Perspectives on International Business special issue “social value creation of MNEs.” The underpinning tenet is that by shifting the domain of international business (IB) research from an exclusive focus on the MNEs’ economic success or failure to the role and responsibility of MNEs in global communities, IB’s contributions can be strengthened.

Findings
A reorientation of the IB disciplinary focus toward global grand challenges will contribute by improving the engagement with other allied disciplines such as political science, sociology and international relations and exchanging ideas and insights with those disciplines, providing a platform to speak to not just business communities but also policy and civil society communities and bring a sophisticated knowledge base to those discussions, and connecting some of our personal interests, beliefs and values with those of our disciplinary research.

Research limitations/implications
The papers covered in this special issue on social value creation underscore the diversity, plurality and richness of IB. In the early days of IB, scholars such as Hymer (1960), Vernon (1971) and others naturally position IBs and MNEs within a broader societal context and were open to exploring the various interactions and cross currents between and among business, government and civil society in the global environment. Against this background, this special issue and its papers thus widen the scope of our field again.

Practical implications
IB scholars may be able to broaden their contributions to include values-based and even normative judgements into their research process.

Social implications
If assumptions and biases are made explicit, critical and normative issues may suitably be incorporated in IB work and thus contribute to tackling grand societal challenges.

Originality/value
The papers discussed in this viewpoint and the “social value creation” special issue more broadly offer contemporary contributions regarding the role and responsibilities of business in the global commons. This is of significant value for further conceptual and empirical work that is critically and societally engaged.
New tools and practices for financing novelty: a research agenda
Authors: Stefani Ulrike , Schiavone Francesco , Laperche Blandine , Burger-Helmchen Thierry 
Published: October 2019

PurposeThe expectations surrounding innovation as the principal mean by which firms gain a sustainable advantage while simultaneously alleviating social problems are tremendous. However, in the process of developing innovation, many small entrepreneurs, SMEs, as well as large firms struggle to access the necessary finances in order to further develop their innovative projects. The purpose of this paper is to underline some of the most recent tools and practices used to finance novelty.Design/methodology/approachThis paper synthetizes some thoughts about the financing of novelty and proposes a research agenda based on trends highlighted in the recent literature.FindingsThis paper pinpoints recent advances in finance applied to the field of innovation. In particular, this paper highlights both promising developments as well as the need for more research in this area in order to untangle the links between creativity and financial support, the financing of innovation in developing countries, accounting and evaluation of ideas.Social implicationsThe importance of developing innovation and easing access to resources has societal implications. The development of education around finance and entrepreneurship, as well as improving literacy of citizens in these fields could yield a more open view on innovation and financial supports in the future.Originality/valueFinancing novelty, evaluating projects and facing uncertainty are among the most difficult decisions investors take. This paper combines many dimensions of innovation and finance to construct an overview of current and future practices within both domains.