bluuebunny/crossref_metadata_2025_split huggingface dataset:
From iron to antibiotics: Identification of conserved bacterial-fungal interactions across diverse partners
Authors: Pierce Emily C. , Morin Manon , Little Jessica C. , Liu Roland B. , Tannous Joanna , Keller Nancy P. , Wolfe Benjamin E. , Pogliano Kit , Sanchez Laura M. , Dutton Rachel J. 
Published: March 2020

ABSTRACTMicrobial interactions are major determinants in shaping microbiome structure and function. Although fungi are found across diverse microbiomes, the mechanisms through which fungi interact with other species remain largely uncharacterized. In this work, we explore the diversity of ways in which fungi can impact bacteria by characterizing interaction mechanisms across 16 different bacterial-fungal pairs, involving 8 different fungi and 2 bacteria (Escherichia coliandPseudomonas psychrophila). Using random barcode transposon-site sequencing (RB-TnSeq), we identified a large number of bacterial genes and pathways important in fungal interaction contexts. Within each interaction, fungal partners elicit both antagonistic and beneficial effects. Using a panel of phylogenetically diverse fungi allowed us to identify interactions that were conserved across all species. Our data show that all fungi modulate the availability of iron and biotin, suggesting that these may represent conserved bacterial-fungal interactions. Several fungi also appear to produce previously uncharacterized antibiotic compounds. Generating a mutant in a master regulator of fungal secondary metabolite production showed that fungal metabolites are key shapers of bacterial fitness profiles during interactions. This work demonstrates a diversity of mechanisms through which fungi are able to interact with bacterial species. In addition to many species-specific effects, there appear to be conserved interaction mechanisms which may be important across microbiomes.
Evolution of an enzyme conformational ensemble guides design of an efficient biocatalyst
Authors: Broom Aron , Rakotoharisoa Rojo V. , Thompson Michael C. , Zarifi Niayesh , Nguyen Erin , Mukhametzhanov Nurzhan , Liu Lin , Fraser James S. , Chica Roberto A. 
Published: March 2020

AbstractThe creation of artificial enzymes is a key objective of computational protein design. Althoughde novoenzymes have been successfully designed, these exhibit low catalytic efficiencies, requiring directed evolution to improve activity. Here, we used room-temperature X-ray crystallography to study changes in the conformational ensemble during evolution of the designed Kemp eliminase HG3 (kcat/KM160 M−1s−1). We observed that catalytic residues were increasingly rigidified, the active site became better pre-organized, and its entrance was widened. Based on these observations, we engineered HG4, an efficient biocatalyst (kcat/KM120,000 M−1s−1) containing active-site mutations found during evolution but not distal ones. HG4 structures revealed that its active site was pre-organized and rigidified for efficient catalysis. Our results show how directed evolution circumvents challenges inherent to enzyme design by shifting conformational ensembles to favor catalytically-productive sub-states, and suggest improvements to the design methodology that incorporate ensemble modeling of crystallographic data.
HIV-1 Vpr-induced Proinflammatory Response and Apoptosis are Mediated through the Sur1-Trpm4 Channel in Astrocytes
Authors: Li Ge , Makar Tapas , Gerzanich Volodymyr , Kalakonda Sudhakar , Ivanova Svetlana , Pereira Edna F. R. , Simard J. Marc , Zhao Richard Y. 
Published: March 2020

AbstractThere are about 38 million people currently living with HIV/AIDS worldwide. Successful treatment with combinational antiretroviral therapies (cART) can eliminate active replicating viruses and prolong lives to nearly normal lifespans. However, the new challenge faced by more than half of those HIV-infected and aging patients is chronic CNS neuroinflammation, which leads to HIV-associated neurocognitive disorders (HAND). While severe and progressive HAND has decreased significantly due to cART, chronic HAND often persists, resulting in high rates of delirium, dementia and depression that could lead to suicide. Indeed, the risk of suicide mortality in HIV-infected persons is significantly higher than in HIV-uninfected counterparts. Nevertheless, the mechanism of neuropathogenesis underlying HAND is not well understood. HAND is typically characterized by HIV-mediated glial neuroinflammation and neurotoxicity. Interestingly, the severity of some HAND does not always correlate with the levels of HIV, but rather with glial activation, suggesting other HIV-associated factors, not the whole virusper se, contribute to those HAND. HIV-1 viral protein R (Vpr) might be one of those viral factors, because Vpr induces neuroinflammation and causes neuronal apoptosis. Theobjectiveof this study was to delineate the specific role(s) of Vpr in activation of host neuroinflammation and neurotoxicity, as well as its contribution to HAND.In this report, we show correlations between HIV expression and activation of proinflammatory markers (TLR4, TNFα, and NFκB) and the Sur1-Trpm4 channel in astrocytes of HIV-infected postmortem human and transgenic mouse brain tissues. We further show that Vpr alone activate the same set of proinflammatory markers in an astrocytic cell line SNB19. Vpr-induced host cell proinflammatory responses result in apoptotic cell death. Together, our data suggest that HIV-1 Vpr-induced proinflammatory response and apoptotic cell death are mediated through the Sur1-Trpm4 channel in astrocytes.
An inverted Caveolin-1 topology defines a novel exosome secreted from prostate cancer cells
Authors: Ariotti Nicholas , Wu Yeping , Okano Satomi , Gambin Yann , Follett Jordan , Rae James , Ferguson Charles , Teasdale Rohan D. , Alexandrov Kirill , Meunier Frederic A. , Hill Michelle M. , Parton Robert G. 
Published: March 2020

ABSTRACTCaveolin-1 (Cav1) expression and secretion is associated with prostate cancer (PCa) disease progression but the mechanisms underpinning Cav1 release remain poorly understood. Numerous studies have shown Cav1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) Cav1 topology. Here we show that Cav1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive Cav1 secretion. Characterization of the isolated vesicles by electron microscopy, single molecule fluorescent microscopy and proteomics reveals they represent a novel class of exosomes ∼40 nm in diameter containing ∼50-60 copies of Cav1 and strikingly, are released via a non-canonical secretory autophagy pathway. This study provides novel insights into a mechanism whereby Cav1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.
Automated design and optimization of multitarget schizophrenia drug candidates by deep learning
Authors: Tan Xiaoqin , Jiang Xiangrui , He Yang , Zhong Feisheng , Li Xutong , Xiong Zhaoping , Li Zhaojun , Liu Xiaohong , Cui Chen , Zhao Qingjie , Xie Yuanchao , Yang Feipu , Wu Chunhui , Shen Jingshan , Zheng Mingyue , Wang Zhen , Jiang Hualiang 
Published: March 2020

AbstractComplex neuropsychiatric diseases such as schizophrenia require drugs that can target multiple G protein-coupled receptors (GPCRs) to modulate complex neuropsychiatric functions. Here, we report an automated system comprising a deep recurrent neural network (RNN) and a multitask deep neural network (MTDNN) to design and optimize multitargeted antipsychotic drugs. The system successfully generates novel molecule structures with desired multiple target activities, among which high-ranking compound3was synthesized, and demonstrated potent activities against dopamine D2, serotonin 5-HT1Aand 5-HT2Areceptors. Hit expansion based on the MTDNN was performed, 6 analogs of compound3were evaluated experimentally, among which compound8not only exhibited specific polypharmacology profiles but also showed antipsychotic effect in animal models with low potential for sedation and catalepsy, highlighting their suitability for further preclinical studies. The approach can be an efficient tool for designing lead compounds with multitarget profiles to achieve the desired efficacy in the treatment of complex neuropsychiatric diseases.Graphical abstract
Gaze-evoked deformations of the optic nerve head in thyroid eye disease
Authors: Fisher Liam K. , Wang Xiaofei , Tun Tin A. , Chung Hsi-Wei , Milea Dan , Girard Michaël J.A. 
Published: March 2020

AbstractPurposeTo assess gaze evoked deformations of the optic nerve head (ONH) in thyroid eye disease (TED), using computational modelling and optical coherence tomography (OCT).MethodsMultiple finite element models were constructed: One model of a healthy eye, and two models mimicking effects of TED; one with proptosis and another with extraocular tissue stiffening. Two additional hypothetical models had extraocular tissue softening or no extraocular tissue at all. Horizontal eye movements were simulated in these models.OCT images of the ONH of 10 healthy volunteers and 1 patient with TED were taken in primary gaze. Additional images were recorded in the same subjects performing eye movements in adduction and abduction.The resulting ONH deformation in the models and human subjects was measured by recording the ‘tilt angle’ (relative antero-posterior deformation of the Bruch’s membrane opening). Effective stress was measured in the peripapillary sclera of the models.ResultsIn our computational models the eyes with proptosis and stiffer extraocular tissue had greater gaze-evoked deformations than the healthy eye model, while the models with softer or no extraocular tissue had lesser deformations, in both adduction and abduction. Scleral stress correlated with the tilt angle measurements.In healthy subjects, the mean tilt angle was 1.46° ± 0.25 in adduction and −0.42° ± 0.12 in abduction. The tilt angle measured in the subject with TED was 5.37° in adduction and −2.21° in abduction.ConclusionsComputational modelling and experimental observation suggest that TED can cause increased gaze-evoked deformations of the ONH.
Aggregated spatio-temporal division patterns emerge from reoccurring divisions of neural stem cells
Authors: Lupperger V. , Marr C. , Chapouton P. 
Published: March 2020

AbstractThe regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms however are poorly understood. In particular it is unclear how the activity of single stem cells is coordinated within the population, or if cells divide in a purely random fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brains revealed weakly aggregated, non-random division patterns in space and time. Analyzing divisions at two timepoints allowed us to infer cell cycle and S-phase lengths computationally. Interestingly, we observed rapid cell cycle re-entries in roughly 15% of newly born NSCs. In agent based simulations of NSC populations, this re-dividing activity sufficed to induce aggregated spatio-temporal division patterns that matched the ones observed experimentally. In contrast, omitting re-divisions lead to a random spatio-temporal distribution of dividing cells. Spatio-temporal aggregation of dividing stem cells can thus emerge from the cell’s history, regardless of possible feedback mechanisms in the population.
My name is bond, Pecorino Bond
Authors: Paoloni Paola , Modaffari Giuseppe , Paoloni Niccolò 
Published: March 2020

PurposeThe aim of this paper is to analyze how “mini-bonds,” an innovative financial tool for Italian small and medium-sized enterprises (SMEs), can contribute to the development and sustainability of the agri-food sector and its local products, such as Pecorino Cheese.Design/methodology/approachThe study was conducted as a qualitative case study applying the CAOS (“characteristics, ambience, organization, start-up”) model. This model makes it possible to describe all variables that affect a company in a given economic context.FindingsIn Sardinia, a small island to the southwest of Italy, there are more than 60,000 agricultural enterprises, 60 percent of which are shepherding operations. Obtaining financial resources is a constant challenge, often related to the uncertainties inherent in seasonal activities. This paper explores how a mini-bond was implemented to promote the development and sustainability of Pecorino Cheese.Research limitations/implicationsLimitations are chiefly related to the short observation period—the bond was first issued in 2018—and to the narrow geographical base of observation.Originality/valueThis research contributes to the expanding body of literature on innovative financial tools for the promotion and development of the local agri-food heritage. It may be useful to practitioners currently researching and developing growth strategies for companies. Existing barriers to credit access are among the most important causes of the lack of development of SMEs, especially in Italy where SMEs represent the principal type of new businesses in the agri-food sector, and their economic success is so dependent on seasonality. In February 2019, the Pecorino case played a role in the Italian government stepping in to avoid the collapse of the price of milk. Future research will focus on the analysis of specific economic results of the financial operations described herein, and will further focus on possibly similar cases of local products making use of innovative financial tools.
Persuasiveness of organic agricultural products
Authors: Chou Feng-sha , Wang Chih-Chien , Lai Ming-Cheng , Tung Chien-Hui , Yang Yann-Jy , Tsai Kuen-Hung 
Published: March 2020

PurposeThe study discusses organic agricultural product persuasion using an empirical survey. This study argued that strong argument persuasive advertising message would trigger individuals' self-reference to the harm of pesticide residue in non-organic agricultural product, which would raise their purchase intention of organic agricultural product.Design/methodology/approachThe present study conducted an empirical investigation in Taiwan by recruiting 527 Taiwanese participants using the convenience sampling procedure. The current research performed structural equation modeling analysis and used LISREL software to report the analytical results.FindingsIndividuals with health consciousness may perceive a high-level risk of non-organic agricultural product, which would raise individuals' fear perception to the harm of pesticide residue. Fear perception will increase individual's purchase intention of organic agricultural product. Results can help industry practitioners benefit from the results by enabling them to develop their advertising strategy for organic food.Originality/valueResults can help industry practitioners benefit from the results by enabling them to develop their advertising strategy for organic food.
Does (un)-related variety promote regional innovation in China? Industry versus services sector
Authors: Yang Nana , Liu Qiming , Qi Yu 
Published: March 2020

PurposeAlthough recent studies have increased attention on the effects of related and unrelated variety on innovation, a Chinese test has until now been missing from the literature. This paper aims to investigate how related and unrelated variety affect regional innovation in Chinese provinces. In particular, emphasis was placed on differentiating the analysis for the industry and services sectors at a detailed sectoral level.Design/methodology/approachThis paper’s sample is composed of 30 provinces in China from 2003 to 2016. Feasible generalized least squares was used to estimate the effects of related and unrelated variety on regional innovation.FindingsThe results show that related variety in all sectors promotes regional innovation, whereas unrelated variety in all sectors does not play a role. In-depth analyses were performed by comparing the industry and services sectors. Only related variety in the industry sector and unrelated variety in the services sector promote regional innovation, whereas unrelated variety in the industry sector exerts a negative effect. After dividing the country into eastern, central and western regions, different findings appear in the sub-samples.Originality/valueThis study contributes to the literature on evolutionary economic geography and innovation by exploring how related and unrelated variety promote regional innovation in a developing country context (China). It also sheds light on the sectoral and regional differences in the influence of related and unrelated variety on regional innovation.
Inequality of opportunity among Indonesian school children
Authors: Indra Indra , Nazara Suahasil , Hartono Djoni , Sumarto Sudarno 
Published: March 2020

Purpose
The purpose of this paper is to analyze the inequality of opportunity among Indonesian school-age children from 2002 to 2012. It focuses on the possibilities of accessing basic needs, such as primary education, secondary education, electricity and clean water.

Design/methodology/approach
This paper used three interrelated indicators, namely, coverage access rate, dissimilarity index and human opportunity index. It also applied Shapley decomposition to measure the contributions of each determinant of inequality opportunities. These data were obtained from the National Household Survey conducted in 2002-2012.

Findings
This study revealed that the level of access to all basic needs, except clean water, was likely to increase with even distribution during the observation period. Moreover, the decomposition results showed that the education of household heads, household income and region (rural-urban) were the main contributors to the total inequality of opportunity.

Originality/value
This study on the inequality of opportunity is interesting, for it is tightly related to inequality of outcome, i.e. income, expenditure and wealth. It is arguable that the inequality of outcome, nowadays, is a reflection of the past inequality in basic opportunities. Thus, the exploration of potential inequality drivers begins to be increasingly important, as it can assist the policymakers in drawing effective policies to repress the increasing trend of future inequality.
Ethical leadership and positive work behaviors: a conditional process model
Authors: Li Chaoping , Bao Yuanjie 
Published: March 2020

PurposeThis study's purpose is to examine ethical leadership's effect on followers' positive work behaviors, as mediated by prosocial motivation and moderated by job autonomy.Design/methodology/approachTwo-wave survey data were collected from 200 Chinese employees working in various industries. A hierarchical regression and a bootstrapping test were used to test the hypotheses.FindingsEthical leadership is positively related to followers' positive work behaviors, and prosocial motivation partially mediates this relationship. Job autonomy moderates the relationship between ethical leadership and prosocial motivation, as well as the indirect effect of ethical leadership on positive work behaviors via prosocial motivation.Research limitations/implicationsThe findings' generalizability is limited because only Chinese employees were investigated and a snowball sampling method was used. Future research should utilize other sampling methods and explore other contexts to determine whether the results can be replicated.Practical implicationsOrganizations should provide employees with greater behavioral discretion to benefit from the positive effects of ethical leadership. They should use selection and job design tools to boost their employees' prosocial motivation.Originality/valueThe extant literature has largely applied the cognitive process approach to link ethical leadership and positive behaviors, treating ethical leadership as a risk-reducing or reciprocity-inducing factor. This study introduces a responsive process approach whereby prosocial motivation is established as a mediator between ethical leadership and positive work behaviors. Also, job autonomy is identified as a boundary condition of ethical leadership's effect.
A framework proposition to identify customer value through lean practices
Authors: Peralta Carla Beatriz da Luz , Echeveste Márcia Elisa , Lermen Fernando Henrique , Marcon Arthur , Tortorella Guilherme 
Published: March 2020

PurposeCustomer value is the key to successful innovation management. This task is considered complex and abstract. For this reason, several models have been proposed to that end, among them, Lean approaches. Lean's background has been applied to value identification, providing many benefits. This paper aims at analyzing the practices employed to identify customer value through Lean approaches.Design/methodology/approachThrough a systematic literature review, the main Lean practices for customer value identification were categorized based on five main streams: (1) customer development, (2) customer value, (3) lean product, (4) lean start-up, and (5) lean innovation. These practices were organized into a framework that addresses value identification based on ideation, value prospection, requirements, construction and measurement, and value delivery.FindingsIn total, 33 practices were found to support capturing the value from the customer's perception. Additionally, a discussion is provided on the complementarity and differences between practices.Originality/valueA framework is proposed to integrate the five streams and the corresponding practices for value identification. The results provide mechanisms that can benefit practitioners to better understand the value demanded by customers during innovation management. In fact, practitioners can use the proposed framework to identify value to customers in a holistic way. Academically, the results gather research on customer value and innovation management to contribute with a novel artifact for customer value identification in operations management using Lean approaches. Finally, a future research agenda on value identification is proposed.
Innovation in the aftermath of downsizing: evidence from the threat-rigidity perspective
Authors: Fernández-Menéndez José , Rodríguez-Ruiz Óscar , López-Sánchez José-Ignacio , Delgado-Piña María Isabel 
Published: March 2020

PurposeThe purpose of this paper is to study how job reductions affect product innovation and marketing innovation in a sample of 2,034 Spanish manufacturing firms in the period 2007–2014.Design/methodology/approachPoisson and logistic regression models with random effects were used to analyse the impact of downsizing on some innovation outcomes of firms.FindingsThe results of this research show that the stressful measure of job reductions may have unexpected consequences, stimulating innovation. However downsizing combined with radical organisational changes such as new equipment, techniques or processes seems to have a negative impact on product and marketing innovation.Originality/valueThis research has two original features. First, it explores the unconventional direction of causality from the planned elimination of jobs to innovation outputs. Secondly, the paper looks at the combined effect of downsizing and other restructuring measures on different types of innovation. Following the threat-rigidity theory, we assume that this combination represents a major threat for survivors that leads to lower levels of product and marketing innovation.