bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bile acids gate dopamine transporter mediated currents
Authors: Romanazzi Tiziana , Zanella Daniele , Cheng Mary Hongying , Smith Behrgen , Carter Angela M. , Galli Aurelio , Bahar Ivet , Bossi Elena 
Published: September 2021

AbstractBile acids (BAs) are molecules derived from cholesterol that are involved in dietary fat absorption. New evidence supports an additional role for BAs as regulators of brain function. Interestingly, sterols such as cholesterol interact with monoamine transporters (MAT), including the dopamine (DA) transporter (DAT) which plays a key role in DA neurotransmission and reward circuitries in the brain. The present study explores interactions of the BA, obeticholic acid (OCA), with DAT and mechanistically defines the regulation of DAT activity via both electrophysiology and molecular modeling. We express murine DAT (mDAT) in Xenopus laevis oocytes and confirm that DA induces an inward current that reaches a steady-state at a negative membrane voltage. Next, we show that OCA triggers an inward current through DAT that is Na+ dependent and not regulated by intracellular calcium. OCA also inhibits the DAT-mediated Li+ leak current, a feature that parallels DA action and indicates direct binding to the transporter. Interestingly, OCA does not alter DA affinity nor the ability of DA to promote a DAT-mediated inward current, suggesting that the interaction of OCA with the transporter is non-competitive, in regard to DA. The current induced by OCA is transient in nature, returning to baseline in the continued presence of the BA. To understand the molecular mechanism of how OCA affects DAT electrical activity, we performed docking simulations. These simulations revealed two potential binding sites that provide important insights into the potential functional relevance of the OCA-DAT interaction. First, in the absence of DA, OCA binds DAT through interactions with D421, a residue normally involved in coordinating the binding of the Na+ ion to the Na2 binding site (Borre et al., 2014;Cheng and Bahar, 2015). Furthermore, we uncover a separate binding site for OCA on DAT, of equal potential functional impact, that is facilitated through the residues DAT R445 and D436. This binding may stabilize the inward-facing open (IFo) state by preventing the re-formation of the IF gating salt bridges, R60-D436 and R445-E428, that are required for DA transport. This study suggests that BAs may represent novel pharmacological tools to regulate DAT function, and possibly, associated behaviors.
Detecting Phytophthora cinnamomi associated with dieback disease on Carya cathayensis using loop-mediated isothermal amplification
Authors: Tong Xiaoqing , Wu Jiayi , Mei Li , Wang Yongjun 
Published: September 2021

AbstractChinese hickory (Carya cathayensis Sarg.) is an economically and ecologically important nut plant in China. Dieback and basal stem necrosis have been observed in the plants since 2016, and its recent spread has significantly affected plant growth and nut production. Therefore, a survey was conducted to evaluate the disease incidence at five sites in Linan County, China. The highest incidence was recorded at the Tuankou site at up to 11.39% in 2019. The oomycete, Phytophthora cinnamomi, was isolated from symptomatic plant tissue and plantation soil using baiting and selective media-based detection methods and identified. Artificial infection with the representative P. cinnamomi ST402 isolate produced vertically elongated discolorations in the outer xylem and necrotic symptoms in C. cathayensis seedlings in a greenhouse trial. Molecular detections based on loop-mediated isothermal amplification (LAMP) specific to P. cinnamomi ST402 were conducted. Result indicated that LAMP detection showed a high coherence level with the baiting assays for P. cinnamomi detection in the field. This study provides the evidence of existence of high-pathogenic P. cinnamomi in the C. cathayensis plantation soil in China and the insights into a convenient tool developed for conducting field monitoring of this aggressive pathogen.
Genetic interaction mapping highlights key roles of the Tol-Pal complex
Authors: Tan Wee Boon , Chng Shu-Sin 
Published: September 2021

AbstractThe conserved Tol-Pal trans-envelope complex is important for outer membrane (OM) stability and cell division in Gram-negative bacteria. It has been proposed to mediate OM constriction during cell division via tethering to the cell wall. Yet, recent studies suggest that the complex has additional roles in OM lipid homeostasis and septal cell wall separation. How the Tol-Pal complex functions to facilitate these many processes is unclear. To gain insights into its role(s), we applied transposon insertion sequencing, and report here a detailed network of genetic interactions with the tol-pal locus in Escherichia coli. We found one positive and >20 negative strong interactions based on fitness. Disruption of genes responsible for osmoregulated periplasmic glucan biosynthesis restores fitness and OM barrier function, but not cell division defects, in tol-pal mutants. In contrast, deletions of genes involved in OM homeostasis and cell wall remodelling give rise to synthetic growth defects in strains lacking Tol-Pal, especially exacerbating OM barrier and/or cell division defects. Notably, the ΔtolA mutant having additional defects in OM protein assembly (ΔbamB) exhibited severe division phenotypes, even under conditions where the single mutants divide normally; this highlights the possibility for OM phenotypes to indirectly influence the cell division process. Overall, our work provides insights into the intricate nature of Tol-Pal function, and reinforces the model that this complex plays crucial roles in cell wall-OM tethering, cell wall remodelling, and in particular, OM homeostasis.
Cross-tissue analysis of allelic X-chromosome inactivation ratios resolves features of human development
Authors: Werner Jonathan M. , Ballouz Sara , Hover John , Gillis Jesse 
Published: September 2021

AbstractX-chromosome inactivation (XCI) is a random, permanent, and developmentally early epigenetic event that occurs during mammalian embryogenesis. We harness these features of XCI to investigate characteristics of early lineage specification events during human development. We initially assess the consistency of X-inactivation and establish a robust set of XCI-escape genes. By analyzing variance in XCI ratios across tissues and individuals, we find that XCI is completed prior to tissue specification and at a time when 6-16 cells are fated for all tissue lineages. Additionally, we exploit tissue specific variability to characterize the number of cells present at the time of each tissue’s lineage commitment, ranging from approximately 20 cells in liver and whole blood tissues to 80 cells in brain tissues. By investigating variance of XCI ratios using adult tissue, we resolve key features of human development otherwise difficult to ascertain experimentally and develop scalable methods easily applicable to future data.
Human iPSC-Based Model Reveals NOX4 as Therapeutic Target in Duchenne Cardiomyopathy
Authors: Duelen Robin , Costamagna Domiziana , Gilbert Guillaume , De Waele Liesbeth , Goemans Nathalie , Desloovere Kaat , Verfaillie Catherine M. , Sipido Karin R. , Buyse Gunnar M. , Sampaolesi Maurilio 
Published: September 2021

ABSTRACTDuchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder, caused by mutations in the Dystrophin gene. Cardiomyopathy is one of the major causes of early death. In this study, we used DMD patient-specific induced pluripotent stem cells (iPSCs) to model cardiomyopathic features in DMD and unravel novel pathological mechanistic insights. Cardiomyocytes (CMs) differentiated from DMD iPSCs showed enhanced premature cell death, due to significantly elevated intracellular reactive oxygen species (ROS) concentrations, as a result of depolarized mitochondria and high NADPH oxidase 4 (NOX4) protein levels. Genetic correction of Dystrophin through CRISPR/Cas9 editing restored normal ROS levels. Application of ROS reduction by N-acetyl-L-cysteine (NAC), partial Dystrophin re-expression by ataluren (PTC124) and enhancing mitochondrial electron transport chain function by idebenone improved cell survival of DMD iPSC-CMs. We show applications that could counteract the detrimental oxidative stress environment in DMD iPSC-CMs by stimulating adenosine triphosphate (ATP) production. ATP could bind to the ATP-binding domain in the NOX4 enzyme, and we demonstrate that ATP resulted in partial inhibition of the NADPH-dependent ROS production of NOX4.Considering the complexity and the early cellular stress responses in DMD cardiomyopathy, we propose to target ROS production and prevent the detrimental effects of NOX4 on DMD CMs as a promising therapeutic strategy.GRAPHICAL ABSTRACTThe use of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from Duchenne muscular dystrophy (DMD) patients to model cardiomyopathic features in DMD and unravel novel pathological mechanistic insights.DMD iPSC-CMs showed accelerated cell death, caused by increased intracellular reactive oxygen species (ROS) levels. By intervention at different target sites, beneficial effects on the mitochondrial membrane potential (ΔΨm) and the expression and ROS-producing activity of the cardiac-specific NADPH-oxidase 4 isoform (NOX4) were observed, resulting in an increased cell survival and function of DMD iPSC-CMs.
Quantitative prediction of variant effects on alternative splicing using endogenous pre-messenger RNA structure probing
Authors: Kumar Jayashree , Lackey Lela , Waldern Justin M. , Dey Abhishek , Mathews David H. , Laederach Alain 
Published: September 2021

AbstractSplicing is a highly regulated process that depends on numerous factors. It is particularly challenging to quantitatively predict how a mutation will affect precursor messenger RNA (mRNA) structure and the subsequent functional consequences. Here we use a novel Mutational Profiling (-MaP) methodology to obtain highly reproducible endogenous precursor and mature mRNA structural probing data in vivo. We use these data to estimate Boltzmann suboptimal ensembles, and predict the structural consequences of mutations on precursor mRNA structure. Together with a structural analysis of recent cryo-EM spliceosome structures at different stages of the splicing cycle, we determined that the footprint of the Bact complex on precursor mRNA is best able to predict splicing outcomes for exon 10 inclusion of the alternatively spliced MAPT gene. However, structure alone only achieves 74% accuracy. We therefore developed a β-regression weighting framework that incorporates splice site strength, structure and exonic/intronic splicing regulatory elements which together achieves 90% accuracy for 47 known and six newly discovered splice-altering variants. This combined experimental/computational framework represents a path forward for accurate prediction of splicing related disease-causing variants.
Competition Between Cell-Cell and Cell-Substrate Adhesion Determines Epithelial Monolayer Architecture in Culture
Authors: Cammarota Christian M. , Dawney Nicole S. , Jia Qingyuan , Jüng Maren M. , Glichowski Joseph A. , Bellomio Philip M. , Fletcher Alexander G. , Bergstralh Dan T. 
Published: September 2021

SummaryOrgan surfaces are lined by epithelial monolayers - sheets of cells that are one-cell thick. This architecture underlies tissue function, and its loss is associated with disease, including cancer. Studies of in-plane epithelial cell behaviors show that a developing epithelium behaves as a fluid in respect to the tissue plane, and can therefore readily adapt to varying mechanical influences during morphogenesis. We asked the question of how monolayer architecture is achieved, and whether it demonstrates the same fluid behavior. To address this problem, we cultured MDCK (Madin-Darby Canine Kidney) cell layers at different densities and timepoints and analyzed their architectures using a novel tool, Automated Layer Analysis (ALAn), which we introduce here. Our experimental and theoretical results lead us to propose that epithelial monolayer architecture is governed by a balance of counteracting forces due to cell-cell and cell-substrate adhesion, and that this balance is influenced by cell density. MDCK cells do not undergo obvious rearrangement along the apical-basal axis; instead, cells that do not contact the substrate aggregate on top of the monolayer. Our findings therefore imply that monolayered architecture is under more rigid control than planar tissue shape in epithelia.
Seasonal phenology of Coffee Berry Borer (Hypothenemus hampeiFerrari) in Hawaii and the influence of weather on flight activity
Authors: Johnson Melissa A. , Manoukis Nicholas C. 
Published: September 2021

AbstractCoffee berry borer (CBB,Hypothenemus hampeiFerrari) is the most serious insect pest of coffee worldwide, yet little is known about its seasonal flight behavior or the effect that weather variables have on its activity. We sampled flying female CBB adults bi-weekly over a three-year period using red funnel traps baited with an alcohol lure at 14 commercial coffee farms on Hawaii Island to characterize seasonal phenology and the influence of five weather variables on flight activity. We captured almost 5 million Scolytid beetles during the sampling period, with 81-93% of the trap catch comprised of CBB. Of the captured non-target beetles, the majority were tropical nut borer, black twig borer and a species ofCryphalus. Two major flight events were consistent across all three years: an initial emergence from January-April that coincided with early fruit development and a second flight during the harvest season from September-December. A linear regression showed a moderate but significant negative relationship between elevation and total trap catch. A generalized additive mixed model (GAMM) revealed that mean daily air temperature has the most significant (positive) effect on CBB flight, with most flight events occurring between 20-26 °C. Mean daily solar radiation also had a significant positive effect, while maximum daily relative humidity negatively influenced flight at values above ∼94%. Flight was positively influenced by maximum daily wind speeds up to ∼2.5 m/s and cumulative rainfall up to 100 mm, after which activity declined. Our findings provide important insight into CBB flight patterns across a highly variable landscape and will serve as a starting point for the development of flight prediction models.
In vivophotopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior
Authors: Ma Xiang , Johnson Desiree A. , He Xinyi Jenny , Layden Aryanna E. , McClain Shannan P. , Yung Jean C. , Banghart Matthew R. 
Published: September 2021

AbstractPhotoactivatable drugs and peptides can drive quantitative studies into receptor signaling with high spatiotemporal precision, yet few are compatible with behavioral studies in mammals. We developed CNV-Y-DAMGO, a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area produced an opioid-dependent increase in locomotion within seconds of illumination. These results demonstrate the power ofin vivophotopharmacology for dynamic studies into animal behavior.
Comparison of modified Karnik-Mendel algorithm-based interval type-2 ANFIS and type-1 ANFIS
Authors: Öztürk Muhammet , Özkol İbrahim 
Published: September 2021

Purpose
This study aims to propose, as the first time, the interval type-2 adaptive network-fuzzy inference system (ANFIS) structure, which is given better results compared to previously presented in the open literature. So, the ANFIS can be used effectively for training of interval type-2 fuzzy logic system (IT2FLS) parameters.

Design/methodology/approach
Karnik–Mendel algorithm (KMA) is modified to use in interval type-2 ANFIS. The modified Karnik–Mendel algorithm (M-KMA) is implemented to change the uncertain ANFIS parameters into known ones. In this way, the interval type-2 ANFIS removes uncertainties of IT2FLS. Therefore, the interval type-2 ANFIS is reduced to a simple one, i.e. less mathematical operation required. Only consequent parameters are trained, and the consequent parameters are chosen in the form of crisp.

Findings
By applying the mentioned procedure, it can be shown that interval type-2 ANFIS has generally better results compared to type-1 ANFIS. However, it was noticed that the worst results obtained in the case of interval type-2 ANFIS are equal to the best result obtained in the case of type-1 ANFIS. Therefore, users in this field can use this approach in solving nonlinear problems.

Practical implications
The interval type-2 ANFIS can be used as controller for highly nonlinear systems such as air vehicles.

Originality/value
As stated in the open literature, it is ineffective to use ANFIS for IT2FLS. In this study, the KMA is modified for IT2FLS, and it is seen that the ANFIS can be used effectively for IT2FLS.
A smart objects library for BIM-based construction site and emergency management to support mobile VR safety training experiences
Authors: Getuli Vito , Capone Pietro , Bruttini Alessandro , Sorbi Tommaso 
Published: September 2021

Purpose
Health and safety training via immersive virtual reality (VR) in the construction sector is still limited to few early adopters despite the benefits it could provide in terms of training effectiveness. To foster its adoption, in this work, the authors address the lack of an organized asset of digital contents dedicated to the production of VR site scenarios that emerged as one of the most limiting factors for the implementation of building information modeling (BIM) and VR for construction workers’ safety training. To improve this critically time-consuming process, a dedicated site object library is proposed.

Design/methodology/approach
The development of the site object library for the production of BIM-based VR safety training experiences followed a four-step process: definition of the object list and categories from the analysis of heterogeneous knowledge sources – construction sectors’ regulations, case studies and site scenarios’ imagery; definition of the object requirements (e.g. information, graphics, sounds, animations and more); design of an object information sheet as a library implementation support tool; and library implementation and validation via collaborative VR sessions.

Findings
This work provides the definition of a structured library of construction site objects dedicated to the production of VR scenarios for safety training comprising 168 items, implemented and validated.

Originality/value
The research contributes to facilitate and standardize the time-consuming contents’ production and modeling process of site scenarios for VR safety training, addressing the lack of a dedicated site object library. Furthermore, the novel library framework could serve as a base for future extensions dedicated to other applications of VR site simulations (e.g. constructability analysis).
The impact of smart specialization strategies on sub-cluster efficiency: simulation exercise for the case of Mexico
Authors: Zárate-Mirón Viviana Elizabeth , Moreno Serrano Rosina 
Published: September 2021

Purpose
This paper aims to evaluate whether the integration of smart specialization strategies (S3) into clusters significantly impacts their efficiency for countries that still do not implement this policy. This study tests three effects: whether the kind of policies envisaged through an S3 strategy impacts cluster’s efficiency; whether this impact changes with the technological intensity of the clusters; to determine which S3 is more suitable for sub-clusters at different levels of technological intensity.

Design/methodology/approach
The Mexican economy is taken as case of study because it has a proper classification of its industries intro Porter’s cluster’s definition but still does not adopt the S3 policy. Through data envelopment analysis (DEA), this study evaluates the cluster’s efficiency increment when variables representing the S3 elements are included.

Findings
The results show that strategies following the S3 had a significant impact in all clusters, but when clusters were classified by technological intensity, the impact on efficiency is higher in clusters in the medium low-tech group.

Practical implications
According to the results in the DEA, it can be concluded that these S3 strategies have the potential to increase the clusters’ productivity significantly. These results make convenient the adoption of the S3 policy by countries that already count with a properly cluster definition.

Originality/value
These findings contribute to the lack of studies that analyze the join implementation of S3 on clusters.
An inductorless piezoelectric energy harvesting interface circuit using gyrator induced voltage flip technique
Authors: Zalke Jitendra B. , Pandey Sandeepkumar R. , Nandanwar Ruchir V. , Pande Atharva Sandeep , Nikam Pravin Balu 
Published: September 2021

Purpose
The purpose of this research paper is to explore the possibility to enhance the power transfer from piezoelectric energy harvester (PEH) source to the load. As the proposed gyrator-induced voltage flip technique (GIVFT) does not require bulky components such as physical inductors, it is easily realizable in small integrated circuits (IC) package thereby offering performance benefits, reducing area overhead and providing cost benefits for constrained self-powered autonomous Internet-of-Things (IoT) applications.

Design/methodology/approach
This paper presents an inductorless interface circuit for PEH. The proposed technique is called GIVFT and is demonstrated using active elements. The authors use gyrator to induce voltage flip at the output side of PEH to enhance the charge extraction from PEH. The proposed technique uses the current-voltage (I-V) relationship of gyrator to get appropriate phasor response necessary to induce the voltage flip at the output of PEH to gain power transfer enhancement at the load.

Findings
The experimental results show the efficacy of the GIVFT realization for enhanced power extraction. The authors have compared their proposed design with popular earlier reported interface circuits. Experimentally measured performance improvement is 1.86×higher than the baseline comparison of full-wave bridge rectifier circuit. The authors demonstrated a voltage flip using GIVFT to gain power transfer improvement in piezoelectric energy harvesting.

Originality/value
To the best of the authors’ knowledge, pertaining to the field of PEH, this is the first reported GIVFT based on the I-V relationship of the gyrator. The proposed approach could be useful for constrained self-powered autonomous IoT applications, and it could be of importance in guiding the design of new interface circuits for PEH.