bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response
Authors: Chiang Michael C. , Nguyen Eileen K. , Papale Andrew E. , Ross Sarah E. 
Published: April 2019

ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.
Cell adhesion molecule interaction with Piezo1 channels is a mechanism for sub cellular regulation of mechanical sensitivity
Authors: Chuntharpursat-Bon E , Povstyan OV , Ludlow MJ , Gaunt HJ , Baxter PD , Beech DJ 
Published: April 2019

AbstractThe discovery of Piezo1 channels as force sensors with roles in the endothelial response to fluid flow has appeared contradictory to earlier work suggesting mediation by a triad of cell adhesion molecules (CD31 and VE-cadherin) and vascular endothelial growth factor receptor 2 (VEGFR2). Here we propose an explanation. Stimulated emission depletion microscopy revealed physical proximity between Piezo1 and CD31 primarily at cell junctions. Förster resonance energy transfer measured by fluorescence lifetime imaging showed that the proteins approached to less than 10 nm. Substitution of a tyrosine residue at the distal C-terminus of CD31 prevented the interaction, suggesting intracellular association. The extracellular N-terminus also interacted, but exclusively at cell junctions. There was proximity between Piezo1 and VE-cadherin but not VEGFR2. Interaction with VE-cadherin was flow-dependent, consistent with additional recruitment after flow-sensing. CD31 suppressed mechanical sensitivity of Piezo1 channels and interacted with N-terminal Piezo1 propeller arms implicated in force sensing. The data suggest partnership between Piezo1 and adhesion molecules for sub cellular tuning of force response.
In-Silico Analysis of nsSNPs Associated with CYP11B2 Gene
Authors: Arooj Anam , Pervez Muhammad Tariq , Gillani Zeeshan , Chohan Tahir Ali , Tayyab Chaudhry M. , Babar Masroor Ellahi , Shah Asma Tufail 
Published: April 2019

AbstractCYP11B2gene is located over the upper layer of the kidney. It produces aldosterone synthase enzyme and thereby has an essential role to balance salt and mineral level in the body. A mutation in this gene can deregulate the production of aldosterone hormone in the body which may lead to many diseases including hypertension and cardiac diseases. To control the excess production of this aldosterone an inhibitor “Fadrozole” is being used which is associated with an active site cavity of CYP11B2. This study has been divided into two parts. In the first part, the four computational tools (SIFT, Polyphen-2, I-Mutant, ConSurf) were used to identify 29 deleterious SNPs out of 1600CYP11B2SNPs. In the second part, five residues (R448G, R141P, W260R, F130S, and F445S) were identified in the active site cavity (out of 29 deleterious CYP11B2 SNPs) at the distance of 5A°. Binding free energy calculation as well as Dynamics simulation techniques were applied to determine the effect of these mutations on the CYP11B2-Fadrozole compound. The results showed thatFadrozolebinding with CYP11B2 became stronger which proved the efficiency of this drug inhibitor with these highly damaging mutations. Our study will be useful for selecting the high priority CYP11B2 mutations, which could be further, investigated in this gene-associated study, for better understanding of the structural and functional aspects of the observed (CYP11B2) protein.
The receptor-like kinases BAM1 and BAM2 promote the cell-to-cell movement of miRNA in the root stele to regulate xylem patterning
Authors: Fan Pengfei , Wang Hua , Xue Hao , Rosas-Diaz Tabata , Tang Weihua , Zhang Heng , Xu Lin , Lozano-Duran Rosa 
Published: April 2019

ABSTRACTXylem patterning in the root is established through the creation of opposing gradients of miRNAs and their targets, enabled by the cell-to-cell spread of the former. The miRNAs involved in xylem patterning, miR165/6, move through plasmodesmata, but how their trafficking is regulated remains elusive. Here, we describe that the receptor-like kinases BAM1/2 are required for the intercellular movement of miR165/6 in the stele and hence proper xylem patterning in the root.
Risk of recurrent pregnancy loss in the Ukrainian population using a combined effect of genetic variants
Authors: Loizidou E. M , Kucherenko A. , Tatarskyy P. , Chernushyn S. , Livshyts G. , Gulkovskyi R. , Vorobiova I. , Antipkin Y. , Gorodna O. , Kaakinen M. A. , Prokopenko I. , Livshits L. 
Published: April 2019

AbstractRecurrent pregnancy loss (RPL) affects nearly 5% of the women of reproductive age. Its heterogeneous and multifactorial nature complicate both diagnosis and treatment, as well as identification of the genetic contribution to RPL. Evidence about the aetiology of RPL is controversial; however, several biological mechanisms have been proposed. Given the current knowledge about the genetic susceptibility to idiopathic RPL, we aimed to evaluate the predictive ability of a combined variant panel to the risk of RPL in the Ukrainian sample of 114 cases and 106 healthy controls. We genotyped variants within the 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21,2.04,P=8.7×10−4). The receiver operator characteristic (ROC) analysis resulted in the area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. In summary, implementation of the GRS approach can help defining women at higher risk to complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in the dissection of biological pathways not hypothesised previously for RPL and further improve the prediction and identification of those at risk for RPL.
Luteal progesterone level correlated with immunotherapy success of patients with repeated implantation failures
Authors: Sefrioui Omar , Madkour Aicha , Bouamoud Nouzha , Kaarouch Ismail , Saadani Brahim , Amzazi Saaïd , Copin Henri , Benkhalifa Moncef , Louanjli Noureddine ,   with the Lorem Ipsum Consortium
Published: April 2019

AbstractImmunotherapy using PBMC administration demonstrated relatively its effectiveness to treat RIF patients but it still unclear to explain some miscarriages. Luteal progesterone level (LPL) issued from corpus luteum after embryo implantation stage could be informative basis data to personalize immunotherapy for RIF patients predicting clinical outcomes. This randomized controlled study included 70 patients undergoing ICSI program presenting at least 3 RIF: 39 for Control of untreated patients and 31 for PBMC-test concerning treated patients with immunotherapy. For PBMC-test group, Peripheral Blood Mononuclear Cells (PBMCs) were isolated from patients on ovulation induction day and cultured three days to be administered to intrauterine cavity of patients two days before fresh embryo transfer. LPL was analyzed at day 15 after embryo transfer and clinical outcomes were calculated including implantation, clinical pregnancy and miscarriage rates. Clinical outcomes were doubly improved after immunotherapy including implantation and clinical pregnancy rates comparing Control versus PBMC-test (10% and 21% vs 24% and 45%). In the other hand, this strategy showed an increase over double in LPL (4ng/ml for Control vs 9ng/ml for PBMC-test) while the latter was correlated to clinical pregnancy. Bypassing the effectiveness of this immunotherapy approach for RIF patients, it is directly correlated to LPL proving the interactive reaction between immune profile of the treated patients and progesterone synthesis by corpus luteum.
Engineering a seven enzyme biotransformation using mathematical modelling and characterized enzyme parts
Authors: Finnigan William , Cutlan Rhys , Snajdrova Radka , Adams Joseph P. , Littlechild Jennifer A. , Harmer Nicholas J. 
Published: April 2019

AbstractMulti-step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi-step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of characterized enzyme parts, we demonstrate the construction of a process model for a seven enzyme, three step biotransformation using isolated enzymes. Enzymes for cofactor regeneration were employed to make thisin vitroreaction economical. Good modelling practice was critical in evaluating the impact of approximations and experimental error. We show that the use and validation of process models was instrumental in realizing and removing process bottlenecks, identifying divergent behavior, and for the optimization of the entire reaction using a genetic algorithm. We validated the optimized reaction to demonstrate that complex multi-step reactions with cofactor recycling involving at least seven enzymes can be reliably modelled and optimized.Significance statementThis study examines the challenge of modeling and optimizing multi-enzyme cascades. We detail the development, testing and optimization of a deterministic model of a three enzyme cascade with four cofactor regeneration enzymes. Significantly, the model could be easily used to predict the optimal concentrations of each enzyme in order to get maximum flux through the cascade. This prediction was strongly validated experimentally. The success of our model demonstrates that robust models of systems of at least seven enzymes are readily achievable. We highlight the importance of following good modeling practice to evaluate model quality and limitations. Examining deviations from expected behavior provided additional insight into the model and enzymes. This work provides a template for developing larger deterministic models of enzyme cascades.
Examining digital video advertising (DVA) effectiveness
Authors: Stewart Kristin , Kammer-Kerwick Matt , Auchter Allison , Koh Hyeseung Elizabeth , Dunn Mary Elizabeth , Cunningham Isabella 
Published: April 2019

Purpose
Marketers are increasing their use of digital strategies and prioritizing digital tactics, although the effectiveness digital video advertising (DVA) has not been examined empirically. The purpose of this research is to suggest that it is useful for advertisers to consider theories of the past to understand the link between product, advertising format and message processing.

Design/methodology/approach
To examine DVA effectiveness, this study utilized a 2-product type (utilitarian vs hedonic) × 2-product involvement (low vs high) x 2-platform (laptop vs mobile) mixed-design. Participants were recruited from a research company, who invited members of their panel to participate in an online experiment.

Findings
DVA for hedonic products resulted in stronger attitudes toward the ad and brand, and intentions to purchase. DVA for low involvement products resulted in stronger purchase intentions and likelihood to opt-in for more information. Moreover, there was an interaction between product category and involvement across all five measures of DVA effectiveness.

Research limitations/implications
Like TV commercials, DVA is more effective when used with low involvement, hedonic products than with high involvement, utilitarian products. Additionally, the device on which the advertisement is viewed impacts the effectiveness of DVA.

Practical implications
Companies promoting high-involvement utilitarian products may consider alternative advertising strategies (e.g. MDAs, apps, websites and advergames), as DVA may not be the most effective ad format.

Originality/value
As technology continues to develop and marketers continue to pursue growing numbers of consumers through digital means and on mobile devices, understanding how device type influences advertising effectiveness is important for media strategy, message placement and marketing metrics. This research takes one step in that direction.
The implications of national and regional long-term orientation on entrepreneurial activity
Authors: Lortie Jason , Barreto Tais , Cox Kevin 
Published: April 2019

PurposeThe purpose of this paper is to investigate the relationship between culture and entrepreneurial activity at both the national and regional levels of analyses. While there has been significant progress in investigating the effects of culture on entrepreneurial activity, most work overlooks the effects that time-orientation may have on national or regional entrepreneurial activity. Specifically, this study argues for the connection between long-term orientation (LTO) and subsequent levels of entrepreneurship such that the more a nation or region is long-term oriented, the higher the subsequent entrepreneurial activity will be.Design/methodology/approachData from the World Value Survey (WVS), which is a global project that measures individuals’ values across 62 countries (World Value Survey, 2011), were used for this project. The final sample consisted of 36,652 individual observations across 29 nations and 262 regions and was analyzed using ecological factor analyses and multilevel modeling.FindingsThe findings suggest that LTO as a cultural dimension does influence entrepreneurship activity levels. The findings also suggest that the effects of LTO at the regional and national levels vary widely. Specifically, the authors find LTO to be positively related to entrepreneurship at the regional, but not national, level of analysis.Originality/valueThe findings reveal important nuances about the implications that the understudied cultural factor of LTO has on entrepreneurial activity across multiple levels of analysis.
Team entrepreneurial competence: multilevel effects on individual cognitive strategies
Authors: Santos Susana C. , Morris Michael H. , Caetano António , Costa Sílvia F. , Neumeyer Xaver 
Published: April 2019

Purpose
The purpose of this paper is to introduce the concept of team entrepreneurial competence, a team-level construct representing the level of shared abilities toward entrepreneurial activities within a new venture team. A multilevel model of the influence of team entrepreneurial competence and team entrepreneurial experience on the cognitive strategies of team members is developed and tested.

Design/methodology/approach
Using a sample of 47 early stage entrepreneurial teams (144 individuals), a set of hypotheses regarding the effect of team entrepreneurial competence on team member reliance on effectual and causal reasoning, together with the moderating effect of team entrepreneurial experience, are tested.

Findings
The results provide support for a positive multilevel association between team entrepreneurial competence and the reliance by team members on both causal and effectual reasoning strategies; members of teams with higher entrepreneurial competence and more entrepreneurial experience are more likely to engage in effectuation.

Research limitations/implications
Understanding how team-level predictors and moderators have a role in determining individual effectuation and causation strategies offers promise in advancing effectuation theory.

Practical implications
Teams develop entrepreneurial competencies that transcend those of individual team members; where teams have more collective entrepreneurial experience, the effect on the tendency of individuals to engage in effectual reasoning is enhanced, which can be beneficial in highly uncertain contexts.

Originality/value
The results of this study are a step forward for effectuation theory, as it demonstrates the role of team-level variables in explaining individual causal and effectual reasoning.
Towards collaborative development culture in local government organisations
Authors: Tuurnas Sanna , Stenvall Jari , Virtanen Petri Juhani , Pekkola Elias , Kurkela Kaisa 
Published: April 2019

Purpose
This paper approaches collaborative governance reform as an empirical phenomenon. The purpose of this paper is to gain insights about the systemic and grassroots level conditions for collaboration, observed from the viewpoint of organisational culture. In this paper, the authors ask what constitutes collaborative development culture in local government organisations?

Design/methodology/approach
The research design is founded on secondary use of quantitative data; a survey targeted to Finnish local government organisations (n=172). The authors analyse what factors the different groups, managers, professionals and politicians consider important for collaborative development culture and how they assess their local government organisations in this regard.

Findings
According to the results, enabling and supporting management, local government personnel’s input and ability to seek external partners are essential for creating a collaborative development culture. Interestingly, despite the recognition of deterring factors by the respondents the results highlight that the supporting and driving factors are more important for creation of collaborative culture, giving an optimistic message to actors trying to enhance collaborative development culture in local government organisations.

Originality/value
The authors examine the collaborative governance reform in a critical way, from the viewpoint of organisational culture. Through the study, it is possible to better understand the reality and readiness for collaboration of local governments in this respect. This is a valuable aspect for increasing both theoretical and practical understanding of the so-called collaborative governance.
Improved biodegradability and tribological performances of mineral lubricating oil by two synthetic nitrogenous heterocyclic additives
Authors: Ding Jianhua , Fang Jianhua , Chen Boshui , Zhang Nan , Fan Xingyu , Zheng Zhe 
Published: April 2019

Purpose
This paper aims to understand the influences of tris (2-hydroxyethyl) isocyanurate oleate and oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester on biodegradability and tribological performances of mineral lubricating oil.

Design/methodology/approach
Tris (2-hydroxyethyl) isocyanurate oleate and oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester were prepared and characterized by Fourier transform infrared spectrometer. The biodegradability and tribological properties of neat oil and its formulations were studied on a tester for fast evaluating biodegradability of lubricants and a four-ball tester, respectively. The worn surfaces were investigated by scanning electron microscope and X-ray photoelectron spectroscope.

Findings
Tris (2-hydroxyethyl) isocyanurate oleate and oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester both improved markedly the biodegradability, the anti-wear properties, friction-reducing properties and extreme pressure properties of base oil. The effect of oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester was better than tris (2-hydroxyethyl) isocyanurate oleate. The improvement of tribological performances was mainly ascribed to the formation of a complicated boundary lubrication film of tris (2-hydroxyethyl) isocyanurate oleate and oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester on the friction surfaces.

Originality/value
This paper has indicated that tris (2-hydroxyethyl) isocyanurate oleate and oleic acid tris (2-hydroxyethyl) isocyanurate phosphate ester effectively improve the biodegradability and tribological performances of mineral lubricating oil. Promoting biodegradation of mineral lubricant by additives is very significant for the development of petroleum-based biodegradable lubricants. These two additives not merely improve the tribological performances; more importantly, they improve the ecological performances.
Multi-level facility location-allocation problem for post-disaster humanitarian relief distribution
Authors: Shavarani Seyed Mahdi 
Published: April 2019

PurposePreviously use of drones as a relief distribution vehicle was studied in several studies where required number of drones and the best locations for the relief centers were investigated. The maximum travel distance of drones without a need to recharge is limited by their endurance. Recharge stations can be used to extend the coverage area of the drones. The purpose of this paper is to find the best topology for both relief centers and recharge stations to cover a large-scale area with minimum and feasible incurred costs and waiting times.Design/methodology/approachA multi-level facility location problem (FLP) is utilized to find the optimum number of relief centers and refuel stations and their locations. It is supposed that the demand occurs according to Poisson distribution. The allocation of the demand is based on nearest neighborhood method. A hybrid genetic algorithm is proposed to solve the model. The performance of the algorithm is examined through a case study.FindingsThe proposed method delivers increased efficiency and responsiveness of the humanitarian relief system. The coverage area of the drones is extended by refuel stations, total costs of the system are reduced and the time to respond an emergency, which is an important factor in survival rate, is significantly decreased.Originality/valueThis study proposes a multi-level FLP to simultaneously account for recharge stations, relief centers and the number of required drones to cover all the demand for relief in a post-disaster period.