bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Axenfeld-Rieger syndrome geneFOXC1contributes to left-right patterning
Authors: Chrystal Paul W. , French Curtis R. , Jean Francesca , Havrylov Serhiy , van Baarle Suey , Peturson Ann-Marie , Xu Pengfei , Crump J. Gage , Pilgrim David B. , Lehmann Ordan J. , Waskiewicz Andrew J. 
Published: May 2020

AbstractNormal body situs requires precise spatiotemporal expression of theNodal-Lefty-Pitx2cascade in the lateral plate mesoderm. The ultimate output of this patterning is establishment of the left-right axis, which provides vital cues for correct organ formation and function. Mutations, deletions and duplications inPITX2andFOXC1lead to the rare genetic disease Axenfeld-Rieger syndrome (ARS). While situs defects are not a recognised feature of ARS, partial penetrance of cardiac septal defects and valve incompetence is observed; both of these congenital heart defects (CHDs) also occur following disruption of left-right patterning. Here we investigated whetherfoxc1genes have a critical role in specifying organ situs. We demonstrate that CRISPR/Cas9 generated mutants for the zebrafish paralogsfoxc1aandfoxc1brecapitulate ARS phenotypes including craniofacial dysmorphism, hydrocephalus and intracranial haemorrhage. Furthermore,foxc1a-/-;foxc1b-/-mutant animals display cardiac and gut situs defects. ModellingFOXC1duplication by transient mRNA overexpression revealed that increasedfoxc1dosage also results in organ situs defects. Analysis of known left-right patterning genes revealed a loss in expression of theNODALantagonistlefty2in the lateral plate mesoderm. Consistently,LEFTY2mutations are known to cause human cardiac situs defects. Our data reveal a novel role for the forkhead-box transcription factorfoxc1in patterning of the left-right axis, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients.Author SummaryThis manuscript investigates the functional consequences of abrogating the activity of Foxc1 (Forkhead Box C1). We demonstrate that loss of zebrafishfoxc1aandfoxc1bresults in phenotypes that resemble human patients with deletions in theFOXC1locus. Notably, such phenotypes include alterations to the morphology of the heart. Investigations into the mechanisms underlying this phenotype led to the discovery that Foxc1 functions as a regulator of left-right patterning. Most components of left-right specification function normally infoxc1a/bmutants, but there is a pronounced loss oflefty2, a known inhibitor of Nodal signaling. This supports a model in which Foxc1 regulates situs of the heart via the regulation of Lefty2.
Antineoplastic kinase inhibitors: a new class of potent anti-amoebic compounds Antineoplastic kinase inhibitors againstEntamoeba histolytica
Authors: Sauvey Conall , Ehrenkaufer Gretchen , Shi Da , Debnath Anjan , Abagyan Ruben 
Published: May 2020

AbstractEntamoeba histolyticais a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960sE. histolyticainfection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, a long treatment course, and the need for an additional drug to prevent cyst-mediated transmission.E. histolyticapossesses a kinome with approximately 300 - 400 members, some of which have been previously studied as potential targets for the development of amoebicidal drug candidates. However, while these efforts have uncovered novel potent inhibitors ofE. histolyticakinases, none have resulted in approved drugs. In this study we took the alternative approach of testing a set of twelve previously FDA-approved antineoplastic kinase inhibitors againstE. histolyticatrophozoitesin vitro. This resulted in the identification of dasatinib, bosutinib, and ibrutinib as amoebicidal agents at low-micromolar concentrations. Next, we utilized a recently developed computational tool to identify twelve additional drugs with human protein target profiles similar to the three initial hits. Testing of these additional twelve drugs led to the identification of ponatinib, neratinib, and olmutinib were identified as highly potent, with EC50values in the sub-micromolar range. All of these six drugs were found to killE. histolyticatrophozoites as rapidly as metronidazole. Furthermore, ibrutinib was found to kill the transmissible cyst stage of the model organismE. invadens. Ibrutinib thus possesses both amoebicidal and cysticidal properties, in contrast to all drugs used in the current therapeutic strategy. These findings together reveal antineoplastic kinase inhibitors as a highly promising class of potent drugs against this widespread and devastating disease.Author SummaryEvery year, nearly a hundred thousand people worldwide die from infection by the intestinal parasiteEntamoeba histolytica, despite the widespread availability of metronidazole as a treatment. Here we report that six anticancer drugs of the kinase inhibitor class possess potent anti-amoebic properties, with one of them killing both actively dividing parasite and its transmissible cysts. These anticancer kinase inhibitors, including the dual-purpose drug with both amoebicidal and cysticidal activities may be used to treat amoebiasis, especially in cancer patients or in life-threatening brain- and liver-infecting forms of the disease.
Bioinformatics approach reveals Nur77-regulated genes common to the central nervous and immune systems
Authors: Olivares-Costa Montserrat , Parada Guillermo , Andrés María Estela 
Published: May 2020

AbstractNeurons and immune cells have similar mechanisms for cell to cell communication. Exists active crosstalk between neurons and immune cells. Neurotransmitters can activate or inhibit immune cells, and cytokines modulate neuronal activity. The transcription factor Nur77 (NR4A1) is highly and transiently induced by several stimuli in neurons and T-lymphocytes, suggesting that Nur77 is involved in the coordination of the genetics response in both cell types. By analyzing publicly available databases, we found Nur77 target genes common to the nervous and immune systems. Functions as cell adhesion and anchoring appear as processes regulated by Nur77 in neurons and immune cells.
Oxygen transport parameter in plasma membrane of eye lens fiber cells by saturation recovery EPR
Authors: Stein N. , Subczynski W. K. 
Published: May 2020

AbstractA probability distribution of rate constants contained within an exponential-like saturation recovery (SR) electron paramagnetic resonance signal can be constructed using stretched exponential function fitting parameters. Previously (Stein et al.Appl. Magn. Reson.2019.), application of this method was limited to the case where only one relaxation process, namely spin-lattice relaxations due to the rotational diffusion of the spin labels in the intact eye-lens membranes, contributed to an exponential-like SR signal. These conditions were achieved for thoroughly deoxygenated samples. Here, the case is described where the second relaxation process, namely Heisenberg exchange between the spin label and molecular oxygen that occurs during bimolecular collisions, contributes to the decay of SR signals. We have further developed the theory for application of stretched exponential function to analyze SR signals involving these two processes. This new approach allows separation of stretched exponential parameters, namely characteristic stretched rates and heterogeneity parameters for both processes. Knowing these parameters allowed us to separately construct the probability distributions of spin-lattice relaxation rates determined by the rotational diffusion of spin labels and the distribution of relaxations induced strictly by collisions with molecular oxygen. The later distribution is determined by the distribution of oxygen diffusion concentration products within the membrane, which forms a sensitive new way to describe membrane fluidity and heterogeneity. This method was validatedin silicoand by fitting SR signals from spin-labeled intact nuclear fiber cell plasma membranes extracted from porcine eye lenses equilibrated with different fractions of air.Statement of SignificanceMulti-exponential spin-lattice relaxation in complex membranous systems can be described by a stretched exponential function that provides a continuous probability distribution of relaxation rates rather than discreet relaxations from separate domains. The stretched exponential function has two fitting parameters, the characteristic spin-lattice relaxation rate (T1str−1) and the stretching parameter (β), obtained without any assumption about the number of membrane domains and their homogeneity. For membranes equilibrated with air, collisions with molecular oxygen provide an additional relaxation pathway for spin labels that depends on the oxygen-diffusion-concentration product in the vicinity of spin labels. This new approach allows separation of membrane fluidity and heterogeneity sensed by motion of lipid spin labels from those described by the translational diffusion of molecular oxygen.
Chronic optogenetic stimulation of hippocampal engrams variably modulates social behaviors in mice
Authors: Doucette Emily , Leblanc Heloise , Monasterio Amy , Cincotta Christine , Grella Stephanie L. , Logan Jesse , Ramirez Steve 
Published: May 2020

AbstractThe hippocampus processes both spatial-temporal information and emotionally salient experiences. To test the functional properties of discrete sets of cells in the dorsal dentate gyrus (dDG), we examined whether chronic optogenetic reactivation of these ensembles was sufficient to modulate social behaviors in mice. We found that chronic reactivation of dDG cells in male mice was sufficient to enhance social behaviors in a female exposure task when compared to pre-stimulation levels. However, chronic reactivation of these cells was not sufficient to modulate group differences in a separate subset of social behaviors, and multi-region analysis of neural activity did not yield detectable differences in immediate-early gene expression or neurogenesis, suggesting a dissociation between our chronic stimulation-induced behavioral effects and underlying neural responses. Together, our results demonstrate that chronic optogenetic stimulation of cells processing valent experiences enduringly and unidirectionally modulates social interactions between male and female mice.
Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway
Authors: Daamen Andrea R. , Bachali Prathyusha , Owen Katherine A. , Kingsmore Kathryn M. , Hubbard Erika L. , Labonte Adam C. , Robl Robert , Shrotri Sneha , Grammer Amrie C. , Lipsky Peter E. 
Published: May 2020

AbstractSARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.Graphical Abstract
Rules of Contact Inhibition of Locomotion for Cells on Suspended Nanofibers
Authors: Singh Jugroop , Camley Brian A. , Nain Amrinder S. 
Published: May 2020

AbstractContact inhibition of locomotion (CIL), in which cells repolarize and move away from contact, is now established as a fundamental driving force in development, repair, and disease biology. Much of what we know of CIL stems from studies on 2D substrates that fail to provide an essential biophysical cue – the curvature of extracellular matrix fibers. We discover rules controlling outcomes of cell-cell collisions on suspended nanofibers, and show them to be profoundly different from the stereotyped CIL behavior known on 2D substrates. Two approaching cells attached to a single fiber do not repolarize upon contact but rather usually migrate past one another. Fiber geometry modulates this behavior: when cells are attached to two fibers, reducing their freedom to reorient, only one of a pair of colliding cells repolarizes on contact, leading to the cell pair migrating as a single unit. CIL outcomes also change when one cell has recently divided and moves with high speed– cells more frequently walk past each other. In collisions with division in the two-fiber geometry, we also capture rare events where a daughter cell pushes the non-dividing cell along the fibers. Our computational model of CIL in fiber geometries reproduces the core qualitative results of the experiments robustly to model parameters. Our model shows that the increased speed of post-division cells may be sufficient to explain their increased walk-past rate. Our results suggest that characterizing cell-cell interactions on flat substrates, channels, or micropatterns is not sufficient to predict interactions in a matrix – the geometry of the fiber can generate entirely new behaviors.SignificanceWhen cells heal a wound or invade a new area, they coordinate their motion. Coordination is often studied by looking at what happens after pairs of cells collide. Post-collision, cells often exhibit contact inhibition of locomotion– they turn around and crawl away from the point where they touched. Our knowledge of repolarization on contact comes from studies on flat surfaces, unlike cells in the body, which crawl along fibers. We discover that cells on single fibers walk past one another– but that cells in contact with multiple fibers stick to one another and move as pairs. This outcome changes to walk-past after cell division. Our experiments and models reveal how the environment regulates cell-cell coordination after contact.
BIM-based life-cycle environmental assessment of prefabricated buildings
Authors: Ji Yingbo , Qi Kai , Qi Yuan , Li Yan , Li Hong Xian , Lei Zhen , Liu Yan 
Published: May 2020

PurposeThis research aims to propose a comparative environmental analysis of conventional and prefabricated construction techniques utilizing a building information modelling (BIM) technique.Design/methodology/approachA set of indicators are selected to assess the environmental emissions throughout the construction life cycle, based on BIM platform. An existing project involving ten apartment buildings in Shanghai is selected as a case study.FindingsThe results reveal that prefabricated construction demonstrates environment-friendly performance with some exceptions of acidification and mineral resource consumption. Environmental impacts can also be further reduced by increasing the projected area ratio and percentage of project prefabrication.Originality/valueOverall, the proposed method can be used to identify relevant environmental merits and for decision-making of appropriate construction techniques in building construction projects.
Factors influencing internet usage for health purposes
Authors: Sumaedi Sik , Sumardjo Sumardjo 
Published: May 2020

PurposeThe objective of this paper is to analyse the simultaneous effect of intention, attitude, knowledge, injunctive norm, descriptive norm, facility access, perceived Internet health information, hedonic motivation, utilitarian motivation, and perceived threat of non-communicable diseases (NCD) on Internet usage for health purposes.Design/methodology/approachThe empirical data were collected through a survey. The respondents of the survey are 369 Jakarta residents. Multiple regression analysis was conducted.FindingsInternet usage for health purposes is significantly affected by intention, knowledge, descriptive norm, and the perceived threat of NCD. Internet usage for health purposes is not influenced by attitude, facility access, perceived Internet health information, hedonic and utilitarian motivation.Research limitations/implicationsThis research was conducted only in Jakarta. It also employed a purposive sampling technique. Future research should be conducted in other locations and used a probability sampling technique.Practical implicationsTo improve the level of Internet usage for health purposes, it is essential to increase the public’s intention to use the Internet for health purposes, their knowledge on Internet usage for health purposes, and their awareness of the dangers of NCD. It is also important to persuade the community influential leaders/persons to use the Internet for health purposes.Originality/valueThis study is the first to develop and test an Internet usage for health purposes model that involves intention, attitude, knowledge, injunctive norm, descriptive norm, facility access, perceived Internet health information, hedonic motivation, utilitarian motivation, and perceived threat of NCD.
Supplier–supplier coopetition and supply chain disruption: first-tier supplier resilience in the tetradic context
Authors: Durach Christian F. , Wiengarten Frank , Choi Thomas Y. 
Published: May 2020

PurposeThe present study considers disruption in the buyer–supplier–supplier triad. This triad has a common second-tier supplier as the disruption source, which gives us the tetradic context. The goal is to advance the knowledge on how a first-tier supplier's resilience against lower-tier disruptive events can be developed through horizontally connecting with the other first-tier supplier and how the buyer can benefit from its first-tier suppliers' resilience capability.Design/methodology/approachData from 33 triads was collected and analyzed.FindingsAs predicted, coopetition between two first-tier suppliers increases the first-tier supplier's capability to be resilient to disruptive events emanating from a lower tier source. However, contrary to initial theorization, the first-tier supplier's resilience capability affects the buyer's performance during disruptive events negatively. With increasing buyer–supplier social bonds, this negative relationship can partly be alleviated.Research limitations/implicationsAnalyzing resilience within a triad to a disruption in the tetradic context reveals unexpected dynamics. Individual supplier's resilience may have a negative impact on the buyer's resilience in certain disruption events.Practical implicationsThe buyer can increase collective suppliers' resilience through establishing horizontal links. To prevent becoming a victim of the supplier's resilience in the event of a second-tier disruption, a buyer needs to become a member of the supplier's relational network.Originality/valueWe propose that resilience can rest with the suppliers. This observation has implications for the buyer when selecting and coordinating suppliers. Further, it considers a context beyond a triad by venturing into the tetradic context. We anticipate more studies in tetrads in future and this study can serve as a bridge.
Digital transforming capability and performance: a microfoundational perspective
Authors: Sousa-Zomer Thayla Tavares , Neely Andy , Martinez Veronica 
Published: May 2020

PurposeDrawing on the literature on dynamic capabilities and digital transformation, this paper conceptualises and investigates the relevant antecedents of an essential capability for digital transformation – the digital transforming capability – and its effect on the competitive advantage of firms.Design/methodology/approachA framework with individual and organisational microfoundations of the digital transforming capability is proposed based on previous research. The digital transforming capability is conceptualised as a second-order construct. The model is tested using data from a broad spectrum of large US companies. Structural equation modelling (SEM) is applied to test the proposed framework.FindingsThe study identifies three main microfoundations that, when combined, build a digital transforming capability (digital-savvy skills, digital intensity and context for action and interaction); in addition, the study tests the relationship between digital transforming capability and firm performance. The results validate the proposed theoretical framework. In addition to proposing relevant microfoundations of the digital transforming capability, we advance knowledge on the performance effects of those microfoundations.Originality/valueThe paper contributes to advancing the understanding of the digital transformation phenomenon by revealing the role of the primary components underlying the digital transforming capability. Yet the mechanisms by which the micro-level aspects are important for digital transformation and organisational outcomes are only suggested by anecdotal evidence. The paper also contributes to ongoing calls for further investigation to extend the understanding of the microfoundations of dynamic capabilities. Finally, by drawing on archival data, this study also contributes to calls to broaden the toolkit used in dynamic capabilities research.
Identification of key variables and constructs in the context of wine tasting room: importance-performance analysis
Authors: Haverila Matti , Haverila Kai , Twyford Jenny Carita 
Published: May 2020

Purpose
Relying on importance–performance theory, this paper uses a distinctive statistical analysis instrument to investigate the importance and performance of crucial wine tasting room constructs and indicators with a purpose to make real and tangible recommendations for wine tasting room managers to improve the winery visit experience.

Design/methodology/approach
The surveys (N = 402) were conducted among 14 wineries in British Columbia, Canada. The data was analysed by using partial least squares structural equation modelling software SmartPLS with importance–performance functionality embedded in it.

Findings
The findings indicate the importance and performance of the service quality constructs, assurance, empathy, reliability, responsiveness, and tangibility and their respective indicator variables in importance–performance map analysis (IPMA). The responsiveness construct showed the highest need for improvement in terms of performance of exogenous service quality constructs in wine tasting rooms. Empathy, value for money and reliability constructs got “no change” recommendation and “tangibility” and “education” recommendation. The assurance construct was not significantly related to customer satisfaction and was not included in the IPMA analysis.

Originality/value
The approach provides an easy to use and visual tool for wineries to assess the importance and performance of the various service quality elements. The tool provides the management of wineries guidance for the identification of strategic areas of service quality improvement.
Ferrofluid lubrication for ball bearings to avoid starvation
Authors: Xu Mancheng , Jin Guanghu , Dai Qingwen , Huang Wei , Wang Xiaolei 
Published: May 2020

Purpose
This paper aims to prevent oil starvation and improve the service life of the rolling bearings.

Design/methodology/approach
A thrust ball bearing with magnetic circuit structure is proposed for ferrofluid lubrication. With the aid of magnetic field, ferrofluid can be maintained in the contact area of rolling bodies to delay lubricant loss. Experiments are performed to ensure the validity of the designed bearing.

Findings
Compared with conventional lubricant, service life of the ferrofluid lubricated bearing can be prolonged under magnetic field. In addition, with a proper magnetic field distribution, lubricant starvation may be limited under the conditions of present experiments.

Originality/value
This work provides a method to control the starved lubrication of rolling bearings with restricted lubricant supply.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-04-2020-0132/