bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is it reasonable to use of a kinship matrix for best linear unbiased prediction?
Authors: Kim Bongsong 
Published: March 2019

AbstractThe linear mixed model (LMM) is characterized to account for the variance-covariance among entities in a population toward calculating the best linear unbiased prediction (BLUP). Animal and plant breeders widely use the LMM because it is perceived that the a BLUP estimate informs an estimated breeding value (EBV), so to speak a combining ability as a parent, obtained by relating each entity to his/her relatives using the variance-covariance. The LMM practice routinely substitutes an external kinship matrix for the variance-covariance. The challenge relevant to the LMM practice is the fact that it is unrealistic to validate the EBVs because the real breeding values are not measurable but conceptual. This unreality actually means that the EBVs are vague. Although some previous studies measured correlations between the EBVs and empirical combining abilities, they are not sufficient to remove the vagueness of EBVs because uncontrollable environmental factors might interfere with phenotypic observations for measuring the combining abilities. To overcome the challenge, this study scrutinized the soundness of the routine LMM practice from the mathematical perspective. As a result, it was demonstrated that the BLUP estimates resulting from the routine LMM practice mislead the breeding values. The genuine BLUP represents the arithmetic means of multiple phenotypic observations per each entity, given all phenotypic observations adjusted to the mean of zero.
Molecular model of the nuclear pore complex reveals a thermoreversible FG-network with distinct territories occupied by different FG motifs
Authors: Huang Kai , Tagliazucchi Mario , Park Sung Hyun , Rabin Yitzhak , Szleifer Igal 
Published: March 2019

SummaryDespite the intensive study of the nuclear pore complex (NPC), its functional core, the central transporter, remains poorly understood. Here, we investigate this unfolded and dynamic part of the NPC using a molecular theory that addresses both entropic and enthalpic effects of the intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Our model shows that the cooperative effect of FG-pairing, specific spacer cohesion, and charge interaction leads to a remarkably elaborate gating structure inside the NPC. In particular, we find sequence-programmed “phase separation” between charge-rich and charge-poor regions, and a polarized electrostatic potential throughout the NPC. The model predicts a thermoreversible FG-network with inhomogeneous FG-pairing fraction in space, which features distinct territories of different types of FG motifs. Our theoretical anatomy of the central transporter reveals a clear sequence-structure-function relationship of the FG-Nups, and explains in a self-consistent way how nucleocytoplasmic transport can be efficient yet specific.
Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model
Authors: Pais Gwendolyn M. , Liu Jiajun , Avedissian Sean N. , Xanthos Theodoros , Chalkias Athanasios , d’Aloja Ernesto , Locci Emanuela , Gilchrist Annette , Prozialeck Walter C. , Rhodes Nathaniel J. , Lodise Thomas P. , Fitzgerald Julie C. , Downes Kevin , Zuppa Athena F. , Scheetz Marc H. 
Published: March 2019

AbstractIntroductionVancomycin and piperacillin tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies.Methods(i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived rat kidney cells (NRK-52E) using an alamarBlue® viability assay. Cells were incubated with antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus VAN 1 mg/mL.ResultsIn the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared to controls (P<0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P<0.001 KIM-1, P<0.05 clusterin). Histopathology was only elevated in the VAN group when compared to TZP as a control (P=0.04). Results were consistent across biomarkers and histopathology suggesting that adding TZP did not worsen VAN induced AKI and may even be protective. In NRK-52E cells, VAN alone caused moderate cell death with high doses (IC5048.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP was not different from VAN alone in NRK-52E cells (P>0.2).ConclusionsVAN+TZP does not cause more kidney injury than VAN alone in a rat model of VIKI or in rat kidney epithelial cells.
CUT&Tag for efficient epigenomic profiling of small samples and single cells
Authors: Kaya-Okur Hatice S. , Wu Steven J. , Codomo Christine A. , Pledger Erica S. , Bryson Terri D. , Henikoff Jorja G. , Ahmad Kami , Henikoff Steven 
Published: March 2019

AbstractMany chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is boundin situby a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.
Base pairing interactions between substrate RNA and H/ACA guide RNA modulate the kinetics of pseudouridylation, but not the affinity of substrate binding by H/ACA small nucleolar Ribonucleoproteins
Authors: Kelly Erin Katelyn , Czekay Dominic Philip , Kothe Ute 
Published: March 2019

AbstractH/ACA small nucleolar ribonucleoproteins (snoRNPs) pseudouridylate RNA in eukaryotes and archaea. They target many RNAs site-specifically through base-pairing interactions between H/ACA guide and substrate RNA. Besides ribosomal RNA (rRNA) and small nuclear RNA (snRNA), H/ACA snoRNPs are thought to also modify messenger RNA (mRNA) with potential impacts on gene expression. However, the base-pairing between known target RNAs and H/ACA guide RNAs varies widely in nature, and therefore the rules governing substrate RNA selection are still not fully understood. To provide quantitative insight into substrate RNA recognition, we systematically altered the sequence of a substrate RNA target by the Saccharomyces cerevisiae H/ACA guide RNA snR34. Time courses measuring pseudouridine formation revealed a gradual decrease in the initial velocity of pseudouridylation upon reducing the number of base pairs between substrate and guide RNA. Changing or inserting nucleotides close to the target uridine severely impairs pseudouridine formation. Interestingly, filter binding experiments show that all substrate RNA variants bind to H/ACA snoRNPs with nanomolar affinity. Next, we showed that binding of inactive, near-cognate RNAs to H/ACA snoRNPs does not inhibit their activity for cognate RNAs, presumably because near-cognate RNAs dissociate rapidly. We discuss that the modulation of initial velocities by the base pairing strength might affect the order and efficiency of pseudouridylation in rRNA during ribosome biogenesis. Moreover, the binding of H/ACA snoRNPs to near-cognate RNAs may be a mechanism to search for cognate target sites. Together, our data provide critical information to aid in the prediction of productive H/ACA guide – substrate RNA pairs.
The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning
Authors: Aime Mattia , Augusto Elisabete , Kouskoff Vladimir , Martin Christelle , Humeau Yann , Chenouard Nicolas , Gambino Frédéric 
Published: March 2019

ABSTRACTSurvival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure 8 kHz tone, and that the activation of BLA-to-FrA axons was the strongest during safe periods in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) as a safety signal impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.
Large-scale kinetic metabolic models ofPseudomonas putidafor a consistent design of metabolic engineering strategies
Authors: Tokic Milenko , Miskovic Ljubisa , Hatzimanikatis Vassily 
Published: March 2019

AbstractA high tolerance ofPseudomonas putidato toxic compounds and its ability to grow on a wide variety of substrates makes it a promising candidate for the industrial production of biofuels and biochemicals. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models. In this work, we developed large-scale kinetic models ofP. putidato predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model ofP. putidaKT2440. We then applied the redGEM and lumpGEM algorithms to reduce the curated iJN1411 model systematically, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism ofP. putida. Using the medium complexity core model as a scaffold, we employed the ORACLE framework to generate populations of large-scale kinetic models for two studies. In the first study, the developed kinetic models successfully captured the experimentally observed metabolic responses to several single-gene knockouts of a wild-type strain ofP. putidaKT2440 growing on glucose. In the second study, we used the developed models to propose metabolic engineering interventions for improved robustness of this organism to the stress condition of increased ATP demand. Overall, we demonstrated the potential and predictive capabilities of developed kinetic models that allow for rational design and optimization of recombinantP. putidastrains for improved production of biofuels and biochemicals.
Elucidation of the viral disassembly switch of tobacco mosaic virus
Authors: Weis Felix , Beckers Maximilian , von der Hocht Iris , Sachse Carsten 
Published: March 2019

AbstractStable capsid structures of viruses protect viral RNA while they also require controlled disassembly for releasing the viral genome in the host cell. A detailed understanding of viral disassembly processes and the involved structural switches is still lacking. Biochemically, this process has been extensively studied using the tobacco mosaic virus model system and carboxylate interactions have been proposed to play a critical part in this process. Here, we present two cryo-EM structures of the helical TMV assembly at 2.1 and 2.0 Å resolution in conditions of high Ca2+concentration at low pH and in water. Based on our atomic models, we identified the conformational details of the disassembly switch mechanism: in high Ca2+/acidic pH environment the virion is stabilized between neighboring subunits through carboxyl groups E95 and E97 in close proximity to a Ca2+binding site. Upon increase in pH and lower Ca2+levels, mutual repulsion of the E95/E97 pair and Ca2+removal destabilize the network of interactions at lower radius and release the switch of virus disassembly. Our TMV structures revealed the conformational details for one of the reference systems of viral assembly/disassembly and provide the mechanistic explanation of a plethora of experimental results that were acquired over decades.Significance StatementTobacco mosaic virus presents the text-book example of virus structure and RNA release from a viral capsid through disassembly. Despite the wealth of structural and biochemical data on the assembly/disassembly properties generated from more than 80 years of research, the atomic-resolution structural details of the proposed conformational changes have not been resolved to date. The here determined high-resolution cryo-EM structures reveal the conformational details of the molecular disassembly switch. When the virus enters the cell, carboxylate repulsion and loss of calcium-ion coordination destabilize the switch region and can trigger RNA release through virus disassembly. The two determined structural states resolve a long-standing question on environment-driven virus disassembly switches.
Chemical screening pipeline for identification of specific plant autophagy modulators
Authors: Dauphinee Adrian N. , Cardoso Catarina , Dalman Kerstin , Ohlsson Jonas A. , Fick Stina Berglund , Robert Stephanie , Hicks Glenn R. , Bozhkov Peter V. , Minina Elena A. 
Published: March 2019

AbstractAutophagy is a major catabolic process in eukaryotes with a key role in homeostasis, programmed cell death and aging. In plants, autophagy is also known to regulate agriculturally important traits such as stress resistance, longevity, vegetative biomass and seed yield. Despite its significance, there is still a shortage of reliable tools modulating plant autophagy. Here we describe the first robust pipeline for identification of specific plant autophagy-modulating compounds. Our screening protocol comprises four phases: (i) high-throughput screening of chemical compounds in cell cultures of Nicotiana tabacum; (ii) confirmation of the identified hits in planta using Arabidopsis thaliana; (iii) further characterization of the effect using conventional molecular biology methods; (iv) verification of chemical specificity on autophagy in planta. The methods detailed here streamline identification of specific plant autophagy modulators and aid in unravelling the molecular mechanisms of plant autophagy.
Driving new narratives: women-leader identities in the automotive industry
Authors: Bullock Christina L. 
Published: March 2019

Purpose
The purpose of this paper is to examine the identity-related work experiences of women in leadership in the US automotive industry. Drawing upon the communication theory of identity’s four identity frames, this study analyzes women’s narratives to better understand their self-concepts, work relationships and activities within larger corporate automotive contexts.

Design/methodology/approach
A qualitative methodology consisting of 16 in-depth interviews with women in leadership in automotive organizations was adopted. Interviews examined women’s perceptions and identities at work, including their daily behaviors, relationships with others and their perceptions of the larger automotive community.

Findings
Findings demonstrate that women in leadership in the automotive industry experience contradictory feelings, messages and interactions that impact their identity perceptions and expectations for performance and achievement in their work settings.

Practical implications
The experiences of women in leadership in US automotive organizations could provide examples of identity-related topics valuable to practitioner fields where women seek relevant, gender-specific, guidance, resources and strategies to advance in their careers.

Social implications
The findings in this study raise awareness about some of the social issues women in leadership face in automotive corporations, including complex identity-related challenges present in their workplaces.

Originality/value
This paper is the first of its type to examine the narratives of women’s career life in leadership in automotive organizations through a communication theory of identity lens. It extends knowledge about female leaders as they navigate the dissonant worlds of achieving higher positions whilst holding membership in a marginalized group.
Determinants of banking consumers’ engagement in post service failure positive word-of-mouth
Authors: Harun Ahasan , Rokonuzzaman Md , Prybutok Gayle , Prybutok Victor R. 
Published: March 2019

PurposeThe purpose of this paper is to develop and examine a theoretical framework that evaluates the effects of banking consumers’ justice perception on their post-complaint mindsets. It also aims to help business strategists to customize service failure management activities to achieve a competitive advantage.Design/methodology/approachTo examine the proposed framework using partial least square structural equation modeling, the authors collected data through a survey. The authors also evaluated the proposed framework through multi-group analysis and importance-performance map analysis (IPMA).FindingsResults show that recovery disconfirmation mediates the relationship between banking consumers’ perception of justice and recovery satisfaction. Moreover, after a service failure, brand equity and loyalty mediate the relationship between recovery satisfaction and positive word-of-mouth behavior. IPMA analysis at the construct level shows that fostering the perception of recovery satisfaction is crucial for creating a positive post-failure impression in the mind of the banking consumer.Practical implicationsFor banking practitioners, the findings of this research provide a strategic blueprint for managing service failure by developing relationships with consumers, thus creating an opportunity to gain competitive advantage.Originality/valueAnchored in the theoretical framework of justice theory (Adams, 1963), expectation disconfirmation theory (Oliver, 1977) and social exchange theory (Kelley and Thibaut, 1978), the research adds to the literature by providing a critical evaluation of how to influence banking consumers’ post-complaint behavior from a more systematic perspective.
Propensity of contracting loans services from FinTech’s in Brazil
Authors: Contreras Pinochet Luis Hernan , Diogo Guilherme Tongnole , Lopes Evandro Luiz , Herrero Eliane , Bueno Ricardo Luiz Pereira 
Published: March 2019

Purpose
Given the large global investments made in FinTechs and the context of Brazilian credit (which has been suffering from the effects of the crisis in the last decade), the purpose of this paper is to study the propensity of consumption of credit services offered by FinTechs of loans. In order to discover the factors that influenced the propensity to apply for FinTech loans, a theoretical model was designed, which was tested by means of a survey given to individuals who might contract loans.

Design/methodology/approach
The final sample consisted of 507 individuals whose data were analyzed through structural equation modeling (SEM), with estimation of partial least squares.

Findings
From the results of the research, it was possible to draw a profile of the FinTechs of Brazilian loans and also to estimate the antecedents of the propensity to utilize this type of service.

Research limitations/implications
The model proposed in this work was developed to measure the propensity to consume in relation to the credit services offered by lending FinTechs.

Practical implications
The consumer should intensify the use of these channels to shape financial products and services to their needs, thereby democratizing access to credit, which is often restricted in quantity and quality by policies of institutions that dominate the Brazilian lending market.

Originality/value
Aspects such as trust, personal innovation, perceived utility, ease of use and social influence, as well as the constructs that precede them like privacy, stigma and transactional distance, explain 41.5 percent of the propensity to use services from lending FinTechs in Brazil.
Analysing the 3PL service provider’s evaluation criteria through a sustainable approach
Authors: Gardas Bhaskar B. , D. Raut Rakesh , Narkhede Balkrishna E. 
Published: March 2019

PurposeThe purpose of this paper is to identify and model the evaluation criteria for the selection of third-party logistics service provider (3PLSP) by an interpretive structural modelling (ISM) approach in the pharmaceutical sector.Design/methodology/approachDelphi technique was used for identifying the most significant criteria, and the ISM method was employed for developing the interrelationship among the criteria. Also, the critical criteria for having high influential power were identified by using the Matrice d’Impacts Croisés Multiplication Appliqués à un Classement analysis.FindingsThe most significant factors, namely, capability of robust supply network/distribution network, quality certification and health safety, service quality and environmental quality certifications, were found to have a high driving power, and these factors demand the maximum attention of the decision makers.Research limitations/implicationsAs the ISM approach is a qualitative tool, the expert opinions were used for developing the structural model, and the judgments of the experts could be biased influencing the reliability of the model. The developed hierarchical concept is proposed to help the executives, decision and policy makers in formulating the strategies and the evaluation of sustainable 3PLSP.Originality/valueIt is an original research highlighting the association between the sustainable 3PLSP evaluation criteria by employing ISM tool in the pharmaceutical industry. This paper will guide the managers in understanding the importance of the evaluation criteria for the efficient selection of 3PLSP.