bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time tracking of complex ubiquitination cascades using a fluorescent confocal on-bead assay
Authors: Koszela Joanna , Pham Nhan T , Evans David , Mann Stefan , Perez-Pi Irene , Shave Steven , Ceccarelli Derek F J , Sicheri Frank , Tyers Mike , Auer Manfred 
Published: February 2018

AbstractThe ubiquitin-proteasome system (UPS) controls the stability, localization and/or activity of the proteome. However, the identification and characterization of complex individual ubiquitination cascades and their modulators remains a challenge. Here, we report a broadly applicable, multiplexed, miniaturized on-bead technique for real-time monitoring of various ubiquitination-related enzymatic activities. The assay, termed UPS-confocal fluorescence nanoscanning (UPS-CONA), employs a substrate of interest immobilized on a micro-bead and a fluorescently labelled ubiquitin which, upon enzymatic conjugation to the substrate, is quantitatively detected on the bead periphery by confocal imaging. UPS-CONA is suitable for studying individual enzymatic activities, including various E1, E2 and HECT-type E3 enzymes, and for monitoring multi-step reactions within ubiquitination cascades in a single experimental compartment. We demonstrate the power of the UPS-CONA technique by simultaneously following ubiquitin transfer from Ube1 through Ube2L3 to E6AP. We applied this multi-step setup to investigate the selectivity of five ubiquitination inhibitors reportedly targeting different classes of ubiquitination enzymes. Using UPS-CONA, we have identified a new activity of a small molecule E2 inhibitor, BAY 11-7082, and of a HECT E3 inhibitor, heclin, towards the Ube1 enzyme. As a sensitive, quantitative, flexible and reagent-efficient method with a straightforward protocol, UPS-CONA constitutes a powerful tool for interrogation of ubiquitination-related enzymatic pathways and their chemical modulators, and is readily scalable for large experiments.
Conservative method for attenuation of Vertical Electrooculogram based on local suppression of artifact templates from ongoing EEG
Authors: Abramov Dimitri M. , Mourão Carlos Alberto , Galhanone Paulo Ricardo , Lazarev Vladimir V. 
Published: February 2018

AbstractBackgroundEye movement during blinking can be a significant artifact in ERP analysis (mainly if ERP is blink-locked). Blinks produce a large positive potential in the vertical electrooculogram (VEOG), spreading towards posterior direction. Two methods are the most frequently used to suppress VEOGs: linear regression to subtract the VEOG signal from each EEG channel and Independent Component Analysis (ICA). However, both lose some EEG information.MethodsThe present algorithm (1) statistically identifies the time position of VEOGs in the frontopolar channels; (2) performs EEG averaging for each channel, which results in ‘blink templates’; (3) subtracts each template from the respective EEG at each VEOG position, only when the linear correlation index between the template and the segment is greater than a threshold L. The signals from twenty subjects were acquired using a behavioral test and were treated using FilterBlink for subsequent ERP analysis. A model was designed to test the method for each subject using twenty copies of the EEG signal from the mid-central channel of the subject (which has almost no VEOG) representing each one of the 20 EEG channels and their respective blink templates. At the same 200 equidistant time points (marks), a signal (2.5 sinusoidal cycles at 1050 ms to emulate an ERP) was mixed with each model channel, along with the respective blink template of that channel, between 500 to 1200 ms after each mark.ResultsAccording to the model, VEOGs interfered with both ERPs and the ongoing EEG mainly on the anterior medial leads, and no significant effect was observed on the mid-central channel (Cz). FilterBlink recovered approximately 90% (at Fp1) to 98% (Fz) of the original ERP and EEG signals to L of 0.1. In the analysis of real signals, the method reduced drastically the VEOG effect on the EEG after ERP and blink-artifact averaging.ConclusionThe method is very simple and effective for VEOG attenuation without significant distortion of the EEG signal and embedded ERPs in all channels.
Spacing of Cue-approach Training Leads to Better Maintenance of Behavioral Change
Authors: Bakkour Akram , Botvinik-Nezer Rotem , Cohen Neta , Hover Ashleigh M. , Poldrack Russell A. , Schonberg Tom 
Published: February 2018

AbstractThe maintenance of behavioral change over the long term is essential to achieve public health goals such as combatting obesity and drug use. Previous work by our group has demonstrated a reliable shift in preferences for appetitive foods following a novel non-reinforced training paradigm. In the current studies, we tested whether distributing training trials over two consecutive days would affect preferences immediately after training as well as over time at a one-month follow-up. In four studies, three different designs and an additional pre-registered replication of one sample, we found that spacing of cue-approach training induced a shift in food choice preferences over one month. The spacing and massing schedule employed governed the long-term changes in choice behavior. Applying spacing strategies to training paradigms that target automatic processes could prove a useful tool for the long-term maintenance of health improvement goals with the development of real-world behavioral change paradigms that incorporate distributed practice principles.
MARGE:Mutation Analysis for Regulatory Genomic Elements
Authors: Link Verena M. , Romanoski Casey E. , Metzler Dirk , Glass Christopher K. 
Published: February 2018

AbstractCell-specific patterns of gene expression are determined by combinatorial actions of sequence-specific transcription factors atcis-regulatory elements. Studies indicate that relatively simple combinations of lineage-determining transcription factors (LDTFs) play dominant roles in the selection of enhancers that establish cell identities and functions. LDTFs require collaborative interactions with additional transcription factors to mediate enhancer function, but the identities of these factors are often unknown. We have shown that natural genetic variation between individuals has great utility for discovering collaborative transcription factors. Here, we introduce MARGE (MutationAnalysis ofRegulatoryGenomicElements), the first publicly available suite of software tools that integrates genome-wide genetic variation with epigenetic data to identify collaborative transcription factor pairs. MARGE is optimized to work with chromatin accessibility assays (such as ATAC-seq or DNase I hypersensitivity), as well as transcription factor binding data collected by ChlP-seq. Herein, we provide investigators with rationale for each step in the MARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation.
Rapid proteotyping reveals cancer biology and drug response determinants in the NCI-60 cells
Authors: Guo Tiannan , Luna Augustin , Rajapakse Vinodh N , Koh Ching Chiek , Wu Zhicheng , Menden Michael P , Cheng Yongran , Calzone Laurence , Martignetti Loredana , Ori Alessandro , Iskar Murat , Gillet Ludovic , Zhong Qing , Varma Sudhir , Schmitt Uwe , Qiu Peng , Sun Yaoting , Zhu Yi , Wild Peter J , Garnett Mathew J , Bork Peer , Beck Martin , Saez-Rodriguez Julio , Reinhold William C. , Sander Chris , Pommier Yves , Aebersold Ruedi 
Published: February 2018

SummaryWe describe the rapid and reproducible acquisition of quantitative proteome maps for the NCI-60 cancer cell lines and their use to reveal cancer biology and drug response determinants. Proteome datasets for the 60 cell lines were acquired in duplicate within 30 working days using pressure cycling technology and SWATH mass spectrometry. We consistently quantified 3,171 SwissProt proteotypic proteins across all cell lines, generating a data matrix with 0.1% missing values, allowing analyses of protein complexes and pathway activities across all the cancer cells. Systematic and integrative analysis of the genetic variation, mRNA expression and proteomic data of the NCI-60 cancer cell lines uncovered complementarity between different types of molecular data in the prediction of the response to 240 drugs. We additionally identified novel proteomic drug response determinants for clinically relevant chemotherapeutic and targeted therapies. We anticipate that this study represents a landmark effort toward the translational application of proteotypes, which reveal biological insights that are easily missed in the absence of proteomic data.
ThePseudomonas aeruginosaLasR quorum-sensing receptor balances ligand selectivity and sensitivity
Authors: McCready Amelia R. , Paczkowski Jon E. , Henke Brad R. , Bassler Bonnie L. 
Published: February 2018

AbstractQuorum sensing is a cell-cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by extracellular signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use thePseudomonas aeruginosaLasR quorum-sensing receptor to explore receptor sensitivity and selectivity. Alteration of LasR amino acid S129 increases ligand selectivity and decreases ligand sensitivity. Conversely, the L130F mutation enhances LasR sensitivity while reducing selectivity. We solve crystal structures of LasR ligand binding domains complexed with non-cognate autoinducers. Comparison to existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop adjacent to the ligand binding site. We show thatP. aeruginosaharboring LasR variants with modified selectivity or sensitivity exhibit altered quorum-sensing responses. We suggest that an evolutionary trade-off between ligand selectivity and sensitivity enables LasR to optimally regulate quorum-sensing traits.
Probing Clostridium difficile infection in innovative human gut cellular models
Authors: Anonye Blessing O. , Hassall Jack , Patient Jamie , Detamornrat Usanee , Aladdad Afnan M. , Schüller Stephanie , Rose Felicity R.A.J. , Unnikrishnan Meera 
Published: February 2018

AbstractInteractions of anaerobic gut bacteria, such as Clostridium difficile, with the intestinal mucosa have been poorly studied due to challenges in culturing anaerobes with the oxygen-requiring gut epithelium. Although gut colonization by C. difficile is a key determinant of disease outcome, precise mechanisms of mucosal attachment and spread remain unclear. Here, using human gut epithelial monolayers co-cultured within dual environment chambers, we demonstrate that C. difficile adhesion to gut epithelial cells is accompanied by a gradual increase in bacterial numbers. Prolonged infection causes redistribution of actin and loss of epithelial integrity, accompanied by production of C. difficile spores, toxins and bacterial filaments. This 2-D dual chamber system was used to examine C. difficile interactions with the commensal Bacteroides dorei, and interestingly, C. difficile growth is significantly reduced in presence of B. dorei. Furthermore, in novel multilayer and 3-D gut models containing a myofibroblast layer, C. difficile adheres more efficiently to epithelial cells, as compared to the 2-D model, leading to a quicker destruction of the epithelium. Our study describes new controlled environment human gut models that enable host-anaerobe and pathogen-commensal interaction studies in vitro.
Rifampicin or capreomycin induced remodelling of theMycobacterium smegmatismycolic acid layer is mitigated in synergistic combinations with cationic antimicrobial peptides
Authors: Man DeDe Kwun-Wai , Kanno Tokuwa , Manzo Giorgia , Robertson Brian D. , Lam Jenny K.W. , Mason A. James 
Published: February 2018

ABSTRACTThe mycobacterial cell wall affords natural resistance to antibiotics. Antimicrobial peptides (AMPs) modify the surface properties of mycobacteria and can act synergistically with antibiotics from differing classes. Here we investigate the response ofMycobacterium smegmatisto the presence of rifampicin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs; distinguished by the presence (D-LAK120-HP13) or absence (D-LAK120-A) of a kink-inducing proline. Using a combination of high-resolution magic angle spinning (HR-MAS) NMR of bacteria, diphenylhexatriene (DPH) fluorescence anisotropy and laurdan emission spectroscopy we show thatM. smegmatisresponds to challenge with rifampicin or capreomycin by substantially altering its metabolism and, in particular, by remodelling the cell envelope. In NMR spectra of bacteria, reductions in intensity for mycolic acid lipid −(CH2)-, -CH3, R2CH-COOH, R2CH-OH and also -CH2-(CH==CH)- and -CH=CH- resonances were observed following challenge with rifampicin and capreomycin, while the latter also caused an increase in trehalose. These changes are consistent with a reduction of trehalose dimycolate and increase of trehalose monomycolate and are associated with an increase in rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampicin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes respectively in these metabolites and did not induce a significant increase in rigidity of the mycolic acid layer. Further, the response to rifampicin or capreomycin was significantly reduced when these were combined respectively with D-LAK120-HP13 and D-LAK120-A, suggesting a possible mechanism for the synergy of these combinations. The remodelling of the mycomembrane inM. smegmatisis therefore identified as an important countermeasure deployed against rifampicin or capreomycin, but this can be mitigated, and rifampicin or capreomycin efficacy potentiated, by combining with AMPs.
Social capital, relational learning, and performance of suppliers
Authors: Sukoco Badri Munir , Hardi Hardi , Qomariyah Alfiyatul 
Published: February 2018

PurposeThe relationship between buyers and suppliers over the years – social practices – facilitate the development of social capital (SC), and it contributes to the relationship performance (RP) for both parties. The purpose of this paper is to examine the mechanisms that transform SC into RP. By exercising the relationship learning (joint sense-making, information sharing, and knowledge integration), this paper proposes that SC will transform into RP.Design/methodology/approachQuantitative study was employed in this study. Questionnaires were distributed to first-tier supplier of Astra Group (Astra International) in Indonesia. In total, 211 questionnaires were used for data analysis in this study.FindingsThe results exhibit that cognitive and structural SC contribute to the development of relational SC. Further, relational SC was positively associated with joint sense-making, which then goes through information sharing, knowledge integration, and finally RP.Research limitations/implicationsThe cross-sectional data in a specific context (a firm) in Indonesia serve as a major limitation of this study. The development of SC and learning as a social process might not be captured well by using the current method – surveys. Furthermore, a major problem is caused by a one-sided survey that depends on the suppliers’ perceptions and judgments of relationship learning and performance.Practical implicationsThe results suggest that managers and other relationship actors would benefit from the competency to develop practices and activities with suppliers regarding developing trust. The trust development is facilitated by having common understanding and interactions regularly, either by participating in formal and/or informal activities with suppliers. Building consensus – joint sense-making, between buyers and suppliers are crucial practices in relationship learning before knowledge sharing and knowledge integration practices are in place. And finally, managers should actively integrate this knowledge in order to increase their RP.Originality/valueThis study empirically tests the supply chain practice view as a new theoretical perspective in the supply chain management literature. It also extends the utilization of social practices – SC – since it is crucial in a buyer-supplier relationship. It also presents that relationship learning is a mechanism that could transform SC into RP, and thus bridge the SC and collaborative learning theory. Finally, this study indicates that inside relational learning, there are sequences of joint sense-making-information sharing-knowledge integration, before it moves on to RP.
External terms-of-trade and labour market imperfections in developing countries
Authors: Chaudhuri Sarbajit , Biswas Anindya 
Published: February 2018

Purpose
Some recent empirical studies have found that developing countries are more prone to external terms-of-trade shocks compared to developed nations. With this background, the purpose of this paper is to the question of whether developing countries possess any built-in mechanism that can cope with external terms-of-trade (TOT) shocks both theoretically and empirically.

Design/methodology/approach
This paper uses a two-sector, full-employment general equilibrium model with endogenous labour market distortion to conduct its theoretical analysis and then uses an annual panel dataset of 13 small developing countries over the recent time period of 2000-2012 to substantiate its theoretical findings.

Findings
Theoretically, this study finds that developing countries possess an inherent shock-absorbing mechanism that stems from their peculiar institutional characteristics and can lessen the gravity of detrimental welfare consequence of exogenous TOT movements. This analytical result has been found to be empirically valid based on a panel dataset of 13 countries from 2000-2012.

Originality/value
The authors’ analyses suggest that that the developing countries should take utmost caution before adopting the policy of labour market reform because these might impair the effectiveness of their in-built shock-absorbing mechanism against adverse international price movements.
Natural disasters, PC supply chain and corporate performance
Authors: Gunessee Saileshsingh , Subramanian Nachiappan , Ning Kun 
Published: February 2018

PurposeThe purpose of this paper is to provide quantitative evidence of natural disasters’ (NDs) effect on corporate performance and studies the mechanisms through which the supply chain moderates and mediates the link.Design/methodology/approachUsing two major NDs as quasi-experiment, namely the 2011 Japanese earthquake-tsunami (JET) and Thai flood (TF), and data over the period 2010Q1-2013Q4, effect of these events on end assemblers’ performance is studied, with a focus on the personal computer (PC) supply chain. The moderating influence of delivery and sourcing – as supply chain flexibility and agility – are examined through end assemblers’ and suppliers’ inventory. The suppliers’ mediating role is captured as disruption in obtaining PC components through their sales.FindingsOnly JET had any negative effect, further quantified as short-term and long-term. The TF instead portrays an insignificant but positive aftermath, which is construed as showing learning from experience and adaptability following JET. Inventory matters, but differently for the two events, and suppliers only exhibit a moderating influence on the assemblers’ disaster-performance link.Originality/valueNDs, as catastrophic vulnerabilities, are distinct from other vulnerabilities in that they are hard to predict and have significant impact. Since little is known about the impact of NDs on firm performance and how supply chain mechanisms moderate or mediate their impact, they should be distinctly modelled and empirically studied from other vulnerabilities. This paper sheds light on supply chain resilience to such events with the role of dynamic capabilities.
An empirical examination of the relationship between globalization, integration and sustainable innovation within manufacturing networks
Authors: Golini Ruggero , Gualandris Jury 
Published: February 2018

PurposeWhile controlling for supply chain effects, the purpose of this paper is to investigate if globalization and collaborative integration within a firm-wide manufacturing network have significant implications for the adoption of sustainable production (SP) and sustainable sourcing (SS) practices at the plant level.Design/methodology/approachThe authors conceptualize SP and SS as process innovations with moderate degrees of innovativeness and apply “Organizational integration and process innovation” theory to build our conceptual model. Then, the authors use primary survey data from 471 assembly manufacturing plants operating in the US, Europe and Asia to test our hypotheses rigorously.FindingsThis research finds that the adoption of SP practices at the plant level is significantly and positively associated with globalization and integration of the firm-wide manufacturing network. On the contrary, the adoption of SS practices is more strongly affected by integration in the external supply chain and benefits from the manufacturing network only indirectly, through the association with SP practices.Originality/valueOperations management literature devoted to sustainability has studied sustainable practices mostly from a risk management angle. Also, there exists contrasting evidence in the operations strategy literature about the positive and negative effects that globalization of a manufacturing network may have on the adoption of sustainable practices at the plant level. Moreover, several studies show how integration with supply chain partners helps manufacturing plants transition into more SP and SS practices; however, related literatures have neglected that collaborative integration within a firm-wide manufacturing network may also help to develop, or adapt to, new sustainable practices. This research represents a first attempt to resolve discordance and unveil the positive effects that manufacturing networks may have on sustainable innovations at the plant level.
Knowledge creation through industry chain in resource-based industry: case study on phosphorus chemical industry chain in western Guizhou of China
Authors: Zhang Wei , Zhang Wenrui 
Published: February 2018

Purpose
This paper aims to provide a theoretical frame and practical experience for understanding and improving knowledge creation in the RIC. This paper proved through an empirical study that knowledge transfer, knowledge assimilation and knowledge sharing between firms in a resource-based industry chain (RIC) have positive influence on knowledge creation.

Design/methodology/approach
A theoretical model covering knowledge transfer, knowledge assimilation, knowledge sharing and knowledge creation is established in this paper. The research object is the phosphorus chemical industry chain in central Guizhou.

Findings
The findings of this paper provide a theoretical frame and practical experience for understanding and improving knowledge creation in the RIC.

Research limitations/implications
The subjective measures of knowledge capacities present a serious limitation. Another limitation is that the authors examined knowledge creation within the context of RIC. The cross-sectional design prevented the authors from studying causal relationships among the variables.

Originality/value
First, it contributes to the knowledge creation of inter-organization literature. Second, it contributes to the studies of knowledge creation in supply chains. Third, this study demonstrates the importance of investigating the strong network embeddedness and industry property of RIC, which have a critic effect on the capabilities of knowledge sharing, transfer and assimilation.