bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of Ebola Virus Matrix Protein Cysteine Residues Increases Binding to Phosphatidylserine through Increased Flexibility of a Lipid Binding Loop
Authors: Johnson Kristen A. , Bhattarai Nisha , Budicini Melissa R. , Shirey Carolyn M. , Baker Sarah Catherine B. , Gerstman Bernard S. , Chapagain Prem P. , Stahelin Robert V. 
Published: March 2018

AbstractThe Ebola virus (EBOV) is a genetically simple negative sense RNA virus with only 7 genes yet it causes severe hemorrhagic fever in humans. The matrix protein VP40 of EBOV is the main driver of viral budding through binding to host plasma membrane lipids and formation of the filamentous, pleomorphic virus particles. To better understand this dynamic and complex process we have asked what the role of two highly conserved cysteine residues are in the C-terminal domain of VP40. Here we report that the mutation of Cys311to alanine increases VP40 membrane binding affinity for phosphatidylserine containing membranes. C311A has a significant increase in binding to PS compared to WT, has longer virus like particles, and displays evidence of increased budding. C314A also has an increase in PS binding compared to WT, however to a lesser extent. The double Cys mutant shares the phenotypes of the single mutants with increased binding to PS. Computational studies demonstrate these Cys residues, Cys311in particular, restrain a loop segment containing Lys residues that interact with the plasma membrane. Mutation of Cys311promotes membrane binding loop flexibility, alters internal VP40 H-bonding, and increases PS binding. To the best of our knowledge, this is the first evidence of mutations that increase VP40 affinity for biological membranes and the length of EBOV virus like particles. Together, our findings indicate these residues are important for membrane dynamics at the plasma membrane via the interaction with phosphatidylserine.
Cellulose biosynthesis inhibition reduces cell cycle activity in a nitrate reductase- and cytokinin-dependent manner
Authors: Gigli-Bisceglia Nora , Engelsdorf Timo , Strnad Miroslav , Vaahtera Lauri , Jamoune Amel , Alipanah Leila , Novák Ondřej , Hejatko Jan , Hamann Thorsten 
Published: March 2018

SummaryDuring growth, development and defense, cell wall integrity needs to be coordinated with cell cycle activity. In Saccharomyces cerevisiae, coordination is mediated by the cell wall integrity maintenance mechanism. In plants, little is known how coordination is achieved.Here we investigated coordination between plant cell wall and cell cycle activity in Arabidopsis thaliana seedlings by studying the impact of cell wall damage (CWD, caused by cellulose biosynthesis inhibition) on cell cycle gene expression, growth, phytohormone (jasmonic acid, salicylic acid, cytokinins) and lignin accumulation.We found root growth and cell cycle gene expression are reduced by CWD in an osmo-sensitive manner. trans-zeatin application suppressed the CWD effect on gene expression. Quantification of cytokinins revealed CWD-induced, osmo-sensitive changes in several cytokinins. Expression of CYTOKININ OXIDASE2/DEHYDROGENASE (CKX2) and CKX3, encoding cytokinin-degrading enzymes, was elevated in CWD-exposed seedlings. Genetic studies implicated NITRATE REDUCTASE1/2 (NIA1/2) in the response to CWD. In nia1/2 seedlings CWD induced neither expression of CKX2/3 and cell cycle genes nor accumulation of jasmonic acid, salicylic acid and lignin.This suggests that CWD causes increased CKX2/3 expression through a NIA1/2-mediated process. Increased CKX expression seems to cause changes in cytokinin levels, leading to reduced cell cycle gene expression.
Sex-specific changes in the aphid DNA methylation landscape
Authors: Mathers Thomas C. , Mugford Sam T. , Percival-Alwyn Lawrence , Chen Yazhou , Kaithakottil Gemy , Swarbreck David , Hogenhout Saskia A. , van Oosterhout Cock 
Published: March 2018

AbstractAphids present an ideal system to study epigenetics as they can produce diverse, but genetically identical, morphs in response to environmental stimuli. Here, using whole genome bisulphite sequencing and transcriptome sequencing of the green peach aphid (Myzus persicae), we present the first detailed analysis of cytosine methylation in an aphid and investigate differences in the methylation and transcriptional landscapes of male and asexual female morphs. We find that methylation primarily occurs in a CG dinucleotide (CpG) context and that exons are highly enriched for methylated CpGs, particularly at the 3’ end of genes. Methylation is positively associated with gene expression, and methylated genes are more stably expressed than un-methylated genes. Male and asexual female morphs have distinct methylation profiles. Strikingly, these profiles are divergent between the sex chromosome and the autosomes; autosomal genes are hypo-methylated in males compared to asexual females, whereas genes belonging to the sex chromosome, which is haploid in males, are hyper-methylated. Overall, we find correlated changes in methylation and gene expression between males and asexual females, and this correlation is particularly strong for genes located on the sex chromosome. Our results suggest that differential methylation of sex-biased genes plays a role in M. persicae sexual differentiation.
Hyperexcitable phenotypes in iPSC-derived neurons from patients with 15q11-q13 duplication syndrome, a genetic form of autism
Authors: Fink James J. , Schreiner Jeremy D. , Bloom Judy E. , Baker Dylan S. , Robinson Tiwanna M. , Lieberman Richard , Loew Leslie M. , Chamberlain Stormy J. , Levine Eric S. 
Published: March 2018

AbstractChromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, Dup15q patients commonly meet the criteria for autism spectrum disorder (ASD) and have a high prevalence of seizures. Here, we explored mechanisms of hyperexcitability in neurons derived from induced pluripotent stem cell (iPSC) lines from Dup15q patients. Maturation of resting membrane potential in Dup15q-derived neurons was similar to neurons from unaffected control subjects, but Dup15q neurons had delayed action potential maturation and increased synaptic event frequency and amplitude. Dup15q neurons also showed impairments in activity-dependent synaptic plasticity and homeostatic synaptic scaling. Finally, Dup15q neurons showed an increased frequency of spontaneous action potential firing compared to control neurons, in part due to disruption of KCNQ2 channels. Together these data point to multiple mechanisms underlying hyperexcitability that may provide new targets for the treatment of seizures and other phenotypes associated with Dup15q.
The Transcriptional landscape of Streptococcus pneumoniae reveals a complex operon architecture and abundant riboregulation critical for growth and virulence
Authors: Warrier Indu , Ram-Mohan Nikhil , Zhu Zeyu , Hazery Ariana , Meyer Michelle M , Opijnen Tim van 
Published: March 2018

AbstractEfficient and highly organized transcription initiation and termination is fundamental to an organism’s ability to survive, proliferate, and quickly respond to its environment. Over the last decade, our simplistic outlook of bacterial transcriptional regulation and architecture has evolved to include stimulus-responsive regulation by untranslated RNA and the formation of alternate transcriptional units. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae by applying a combination of high-throughput RNA-sequencing techniques. Our study reveals a complex transcriptome wherein environment-respondent alternate transcriptional units are observed within operons stemming from internal transcription start sites (TSS) and transcription terminators (TTS) suggesting that more fine-tuning of regulation occurs than previously thought. Additionally, we identify many putative cis-regulatory RNA elements and riboswitches within 5’-untranslated regions (5’-UTR) of genes. By integrating TSSs and TTSs with independently collected RNA-Seq datasets from a variety of conditions, we establish the response of these regulators to changes in growth conditions and validate several of them. Furthermore, to determine the importance of ribo-regulation by 5’-UTR elements for in vivo virulence, we show that the pyrR regulatory element is essential for survival, successful colonization and infection in mice suggesting that such RNA elements are potential drug targets. Importantly, we show that our approach of combining high-throughput sequencing with in vivo experiments can reconstruct a global understanding of regulation, but also pave the way for discovery of compounds that target (ribo-) regulators to mitigate virulence and antibiotic resistance.
Profiling of pluripotency factors in individual stem cells and early embryos
Authors: Hainer Sarah J. , Bošković Ana , Rando Oliver J. , Fazzio Thomas G. 
Published: March 2018

SUMMARYMajor cell fate decisions are governed by sequence-specific transcription factors (TFs) that act in small cell populations within developing embryos. To understand how TFs regulate cell fate it is important to identify their genomic binding sites in these populations. However, current methods cannot profile TFs genome-wide at or near the single cell level. Here we adapt the CUT&RUN method to profile chromatin proteins in low cell numbers, mapping TF-DNA interactions in single cells and individual pre-implantation embryos for the first time. Using this method, we demonstrate that the pluripotency TF NANOG is significantly more dependent on the SWI/SNF family ATPase BRG1 for association with its genomic targets in vivo than in cultured cells—a finding that could not have been made using traditional approaches. Ultra-low input CUT&RUN (uliCUT&RUN) enables interrogation of TF binding from low cell numbers, with broad applicability to rare cell populations of importance in development or disease.
Click-xylosides overcome neurotoxic effects of reactive astrocytes and promote neuronal growth in a cell culture model of brain injury
Authors: Vimal Swarup , Kuberan Balagurunathan 
Published: March 2018

AbstractAstrocytes, upon activation in response to brain injury, play a critical role in protecting neurons by limiting inflammation through the excessive secretion of many soluble factors, such as, chondroitin sulfate proteoglycans (CSPGs). Unfortunately, excessive CSPGs paradoxically prohibit neuronal recovery and growth, and eventually constitute a scar tissue. Many studies have attempted to overcome this barrier through various molecular approaches including the removal of inhibitory CSPGs by applying chondroitinase enzymes. In this study, we examined whether click-xylosides, which serve as primers of glycosaminoglycan (GAG) biosynthesis, can compete with endogenous inhibitory CSPGs for GAG assembly by serving as decoy molecules and thereby potentially reverse reactive astrocyte mediated neuronal growth inhibition. We investigated the axonal growth of hippocampal neurons in the presence of xyloside treated and untreated reactive astrocyte-conditioned media as a model recapitulating brain injury. Click-xylosides were found to interfere with the GAG biosynthetic machinery in astrocytes and reduced the amount of secreted inhibitory CSPGs by competing with endogenous assembly sites. The extent of underglycosylation was directly related to the outgrowth of hippocampal neurons. Overall, this study suggests that click-xylosides are promising therapeutic agents to treat CNS injuries and warrants further in vivo investigations.
Aversive conditioning in oddball paradigm modulates multisensory integration, attention and emotional processing
Authors: Pavlov Yuri G. , Kotchoubey Boris 
Published: March 2018

AbstractThe nature of cortical plasticity in the course of learning is one of the most intriguing questions of the modern cognitive neuroscience. Aversive conditioning is a type of associative learning produced by continuous pairing of neutral and aversive stimuli. Aversive conditioning and electroencephalography together provide a good framework for expanding our knowledge about fast learning-related cortical changes. In our experiment we tested a novel paradigm to study associative learning where aversive conditioning was combined with passive oddball. We employed conditioned auditory neutral stimuli and unconditioned aversive electrical shocks and used time-frequency, connectivity and event-related potentials (ERP) analyses to explore their interaction. First, we observed changes in the cortical activity in the form of conditioning-induced multisensory integration. The integration manifested itself in (1) desynchronization of lower beta activity in the contralateral to expected electrical shocks hemisphere and (2) enhanced functional connectivity between auditory and somatosensory cortex in the gamma frequency band. Second, we found a larger amplitude of P3a and the late posterior positivity (LPP) components of ERP to conditioned stimuli, which may be related to increased attentional and emotional significance of these stimuli. Our results reproduced and extended previous findings about multisensory integration in classical conditioning and demonstrated the improved discriminability of ERP responses through incorporation of the oddball paradigm in associative learning.
A comprehensive automated pipeline for human microbiome sampling, 16S rRNA gene sequencing and bioinformatics processing
Authors: Hugerth LW , Seifert M , Pennhag AAL , Du J , Hamsten MC , Schuppe-Koistinen I , Engstrand L 
Published: March 2018

ABSTRACTThe advent of affordable high-throughput DNA sequencing has opened up a golden age of studies in the human microbiome. In order to understand the role of the human microbiota, standardized methods for large-scale, population-level studies are needed to avoid underpowered or poorly designed studies. The biggest bottlenecks to population-level microbiomics are sample collection, storage and DNA extraction. Here, we describe a flexible automated approach to process intestinal biopsies, fecal samples and vaginal swabs from sample collection to OTU table. We have evaluated storage conditions, DNA extraction methods, PCR strategies and bioinformatic pipelines for these three sample types, and present here a set of guidelines and best practices for each of these steps.
Phosphoserine acidic cluster motifs in the cytoplasmic domains of transmembrane proteins bind distinct basic regions on the μ subunits of clathrin adaptor protein complexes
Authors: Singh Rajendra , Stoneham Charlotte , Lim Christopher , Jia Xiaofei , Guenaga Javier , Wyatt Richard , Wertheim Joel O. , Xiong Yong , Guatelli John 
Published: March 2018

AbstractProtein trafficking in the endosomal system involves the recognition of specific signals within the cytoplasmic domains (CDs) of transmembrane proteins by clathrin adaptors. One such signal is the phosphoserine acidic cluster (PSAC), the prototype of which is in the endoprotease Furin. How PSACs are recognized by clathrin adaptors has been controversial. We reported previously that HIV-1 Vpu, which modulates cellular immunoreceptors, contains a PSAC that binds to the µ subunits of clathrin adaptor protein (AP) complexes. Here, we show that the CD of Furin binds the µ subunits of AP-1 and AP-2 in a phosphorylation-dependent manner. Moreover, we identify a PSAC in a cytoplasmic loop of the cellular transmembrane Serinc3, an inhibitor of the infectivity of retroviruses. The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the µ subunits in vitro. The sites of these serines vary among mammals in a manner consistent with host-pathogen conflict, yet the Serinc3-PSAC seems dispensible for anti-HIV activity and for counteraction by HIV-1 Nef. The CDs of Vpu, Furin, and the PSAC-containing loop of Serinc3 each bind the μ subunit of AP-2 (µ2) with similar affinities, but they appear to utilize different basic regions on µ2. The Serinc3 loop requires a region previously reported to bind the acidic plasma membrane lipid phosphatidylinositol-4,5-bisphosphate. These data suggest that the PSACs within different proteins recognize different basic regions on the µ surface, providing the potential to inhibit the activity of viral proteins without necessarily affecting cellular protein trafficking.
Abusive supervision: a framework of developmental solutions to this workplace menace
Authors: Pradhan Sajeet , Jena Lalatendu Kesari 
Published: March 2018

PurposeThe purpose of this paper is to offer a preventive framework that will neutralize the pernicious effects of abusive supervision in organizations.Design/methodology/approachBased on the extant literature, the study takes an exploratory viewpoint of the harmful effects of abusive supervision on subordinates and offers intervention strategies that will provide both preemptive measures and reactive recourse for the victim.FindingsAs abusive supervision cannot be completely eradicated from workplace, the study offers a preventive framework (based on the stress and health management models of Parkes and Sparkes, 1998; Quick, 1999) that will counter abusive supervision at different points in time and through different interventions (psychosocial and socio-technical).Originality/valueThe paper is the first of its kind as it offers a comprehensive solution (both proactive and reactive) to the problems associated with abusive supervision. Previous studies have purely focused on various coping mechanisms for the victim.
Cross-border branching in the Latin American banking sector
Authors: Fávero Luiz Paulo Lopes , dos Santos Marco Aurélio , Serra Ricardo Goulart 
Published: March 2018

Purpose
Branching is not the only way for foreign banks to enter a national market, and it is impractical when there are informational and cultural barriers and asymmetries among countries. The purpose of this paper is to analyze the determinants of cross-border branching in the Latin American banking sector, a region with regulatory disparity and political and economic instability, offering elements to a grounded strategic decision.

Design/methodology/approach
This study uses data from six Latin American countries. To account for the preponderance of zero counts, classes of zero-inflated models are applied (Poisson, negative binomial, and mixed). Model fit indicators obtained from differences between observed and estimated counts are used for comparisons, considering branches in each region established by banks from every other foreign region of the sample.

Findings
Branching by foreign banks is positively correlated with the population, GDP per capita, household disposable income, and economic freedom score of the host country. The opposite holds for the unemployment rate and entry regulations of the host country.

Originality/value
Few paper address cross-border banking in emerging economies. This paper analyzes cross-border branching in Latin America in the context of the current financial integration and bank strategy. Econometrically, its pioneering design allows modeling of inflation of zeros, over-dispersion, and the multilevel data structure. This design allowed testing of a novel country-level variable: the host country’s economic freedom score.
Profiling emerging market investors: a segmentation approach
Authors: Kumar Satish , Goyal Nisha , Basu Rituparna 
Published: March 2018

Purpose
The purpose of this paper is to obtain a market-oriented approach to segment individual investors in terms of their attitudes and behaviour towards investment. It also attempts to understand the impact of certain demographic variables like gender, age and education on the behaviour of individual investors in the emerging urban Indian market.

Design/methodology/approach
A structured questionnaire was used to obtain a total of 340 valid responses which were collected from March 2016 to August 2016. Factor analysis was used to explore the components. Based on these components, cluster analysis was used to identify different subgroups. Statistical techniques, namely, t-test, analysis of variance and Fisher’s least significant difference test were used to examine the impact of demographic variables.

Findings
Factor analysis displayed five components, namely, interest in financial matters, anxiety for money, logical decisions, concern for future and spending tendency. Cluster analysis indicates that individuals can be divided into five clusters based on these components. It further substantiates that gender and education have a significant association with each subgroup.

Research limitations/implications
Individual investor segments that were identified and profiled may provide an opportunity for advisors, financial analysts, organisations and investors to improve investment decision making. In this way, financial service firms can identify and provide services based on group-specific needs.

Originality/value
To the best of the authors’ knowledge, this study is the first of its kind to segment Indian investors into different homogeneous groups based on their attitude and behaviour towards financial matters.
Intention to use e-banking services in the Jordanian commercial banks
Authors: Yaseen Saad Ghaleb , El Qirem Ihab Ali 
Published: March 2018

PurposeThe purpose of this paper is to investigate the essential factors influencing the adoption and use of e-banking services as perceived by customers of the Jordanian commercial banks.Design/methodology/approachThis paper adapts and modifies the unified theory of acceptance and use of the technology model. Modifications were made to explain intention to use e-banking services.FindingsThe modified model explained 0.887 of behavior intention variance and 0.516 percent of the intended degree of e-banking services use variance. Three constructs are found to be good predictors: effort expectancy (EE), social influence, and perceived e-banking services quality. Performance expectancy and hedonic motivation are not significant predictors. However, all three predictors were significantly moderated by age only.Research limitations/implicationsAs with any research in the field of IT adoption and consumer behavior, researchers should take into consideration the generalization of their empirical findings. The generalization could be enhanced if future research uses the Jordanian baking sector which includes Jordanian and non-Jordanian banks. Finally, the current research findings are based on the cross-sectional research method. Taking this fact into consideration, the relation between intention and actual use may raise questions. One solution is to study intention and actual use at different points in time by conducting longitudinal research to access and test the research hypotheses.Practical implicationsManagers need to focus on promoting e-banking services in terms of consumer’s EE, social influence, and e-banking service quality. Since young consumers are early adopters, Jordanian banks need to introduce added entertainment values for youth and extra convenience for older consumers.Originality/valueThe main contributions revolve around developing a better understanding of the essential factors influencing the adoption and use of e-banking services. This research incorporates a new variable: perceived e-banking quality. Thus, the proposed model provides better explanatory power than previous research.