bluuebunny/crossref_metadata_2025 huggingface dataset:
Current and Future Costs of Intractable Conflicts—Can They Create Attitude Change?
Authors: Rosler Nimrod , Hameiri Boaz , Bar-Tal Daniel , Christophe Dalia , Azaria-Tamir Sigal
Published: May 2021

Members of societies involved in an intractable conflict usually consider costs that stem from the continuation of the conflict as unavoidable and even justify for their collective existence. This perception is well-anchored in widely shared conflict-supporting narratives that motivate them to avoid information that challenges their views about the conflict. However, since providing information about such major costs as a method for moderating conflict-related views has not been receiving much attention, in this research, we explore this venue. We examine what kind of costs, and under what conditions, exposure to major costs of a conflict affects openness to information and conciliatory attitudes among Israeli Jews in the context of the intractable Israeli–Palestinian conflict. Study 1 (N = 255) revealed that interventions based on messages providing information on mental health cost, economic cost, and cost of the conflict to Israeli democracy had (almost) no significant effect on perceptions of the participants of these prices, openness to new information about the conflict, or support for conciliatory policies. However, the existing perceptions that participants had about the cost of the conflict to Israeli democracy were positively associated with openness to alternative information about the conflict and support for conciliatory policies. Therefore, in Study 2 (N = 255), we tested whether providing information about future potential costs to the two fundamental characteristics of Israel, a democracy or a Jewish state, created by the continuation of the conflict, will induce attitude change regarding the conflict. The results indicate that information on the future cost to the democratic identity of Israel significantly affected the attitude of the participants regarding the conflict, while the effect was moderated by the level of religiosity. For secular participants, this manipulation created more openness to alternative information about the conflict and increased support for conciliatory policies, but for religious participants, it backfired. We discuss implications for the role of information about losses and the relationship between religiosity and attitudes regarding democracy and conflict.
Adverse Childhood Experiences and Mindfulness in Chinese College Students During the COVID-19 Pandemic
Authors: Huang Chienchung , Yang Meifen , Geng Yun , Chen Yafan , Cheung Shannon P. , Deng Guosheng , Dong Qiang , Hu Hongwei , Hua Kai , Liao Jinyu , Tan Yuanfa , Tu Bin , Wang Enjian , Yu Zhihong , Zhang Congcong , Zhang Shuyan , Zhuo Gaosheng
Published: May 2021

Mindfulness has been found to have many positive effects on life outcomes, including mental health and educational achievement. However, less is known about the antecedents of mindfulness, particularly in Chinese college students. This study examines the effect of adverse childhood experiences (ACEs) on mindfulness among Chinese college students in September 2020, during the COVID-19 pandemic. We hypothesized that ACEs negatively affected students' mindfulness. The data were collected from 1,871 college students from 12 colleges across China. The results aligned with our hypothesis that ACEs was negatively associated with mindfulness. In particular, emotional abuse and neglect in childhood appear to have the most negative effects on mindfulness compared to other dimensions of ACEs such as physical abuse and household challenges.
Impending Transition From Pediatric to Adult Health Services: A Qualitative Study of the Experiences of Adolescents With Eating Disorders and Their Caregivers
Authors: Nadarajah Ajantha , Dimitropoulos Gina , Grant Christina , Webb Cheryl , Couturier Jennifer
Published: May 2021

Background: There is a dearth of research that identifies pediatric to adult health care transition practices that yield positive outcomes for young people with eating disorders (EDs). Further, adolescent and caregiver perspectives are poorly understood and underrepresented in the literature. The purpose of this study, focused on the impending transition from pediatric to adult health services, was twofold: (a) to identify adolescent and caregiver perspectives of barriers and facilitators of a successful transition for adolescents with EDs; and (b) to understand adolescent and caregiver suggestions of interventions for a successful transition.

Design/Method: We recruited five adolescents with EDs who were about to be transferred out of pediatric care as well as their caregivers. We conducted a qualitative study in accordance with the principles of interpretive description. Through conducting semi-structured, in-depth interviews with adolescents and caregivers, we investigated their knowledge about health system transitions and anticipated experiences. We identified participants' perceptions of barriers and facilitators regarding a successful transition, as well as their recommendations to improve the transfer of care.

Results: Participants possessed a limited understanding of transition processes despite the fact that they were about to be transferred to adult care. From our analyses, the following themes were identified as barriers during the transition process: re-explaining information to adult healthcare providers, lack of professional support while waiting for uptake into the adult health system, and late timing of transition of care discussions. Both adolescents and caregivers expressed that involvement of parents and the pediatric healthcare team helped to facilitate a successful transfer of care. In addition, participants expressed that the implementation of a Transition Coordinator and Transition Passport would be helpful in facilitating a seamless transfer between systems of care.

Discussion: These findings demonstrate a significant gap in the system and highlight the importance of developing interventions that facilitate a successful transition. The themes that emerged from this study can inform the development of interventions to facilitate a coordinated transition from pediatric to adult health services for adolescents with EDs.
Adaptive and Energy-Efficient Optimal Control in CPGs Through Tegotae-Based Feedback
Authors: Zamboni Riccardo , Owaki Dai , Hayashibe Mitsuhiro
Published: May 2021

To obtain biologically inspired robotic control, the architecture of central pattern generators (CPGs) has been extensively adopted to generate periodic patterns for locomotor control. This is attributed to the interesting properties of nonlinear oscillators. Although sensory feedback in CPGs is not necessary for the generation of patterns, it plays a central role in guaranteeing adaptivity to environmental conditions. Nonetheless, its inclusion significantly modifies the dynamics of the CPG architecture, which often leads to bifurcations. For instance, the force feedback can be exploited to derive information regarding the state of the system. In particular, theTegotaeapproach can be adopted by coupling proprioceptive information with the state of the oscillation itself in the CPG model. This paper discusses this policy with respect to other types of feedback; it provides higher adaptivity and an optimal energy efficiency for reflex-like actuation. We believe this is the first attempt to analyse the optimal energy efficiency along with the adaptivity of the Tegotae approach.
Predicting Key Grassland Characteristics from Hyperspectral Data
Authors: Jackman Patrick , Lee Thomas , French Michael , Sasikumar Jayadeep , O’Byrne Patricia , Berry Damon , Lacey Adrian , Ross Robert
Published: May 2021

A series of experiments were conducted to measure and quantify the yield, dry matter content, sugars content, and nitrates content of grass intended for ensilement. These experiments took place in the East Midlands of Ireland during the Spring, Summer, and Autumn of 2019. A bespoke sensor rig was constructed; included in this rig was a hyperspectral radiometer that measured a broad spectrum of reflected natural light from a circular spot approximately 1.2 m in area. Grass inside a 50 cm square quadrat was manually collected from the centre of the circular spot for ground truth estimation of the grass qualities. Up to 25 spots were recorded and sampled each day. The radiometer readings for each spot were automatically recorded onto a laptop that controlled the sensor rig, and ground truth measurements were made either on-site or within 24 h in a wet chemistry laboratory. The collected data was used to build Partial Least Squares Regression (PLSR) predictive models of grass qualities from the hyperspectral dataset, and it was found that substantial relationships exist between the spectral reflectance from the grass and yield (r2 = 0.62), dry matter % (r2 = 0.54), sugar content (r2 = 0.54) and nitrates (r2 = 0.50). This shows that hyperspectral reflectance data contains substantial information about key grass qualities and can form part of a broader holistic data-driven approach to provide accurate and rapid predictions to farmers, agronomists, and agricultural contractors.
Mechanical Properties and Thermal Conductivity of Fly Ash-Based Geopolymer Foams with Polypropylene Fibers
Authors: Agustini Ni Komang Ayu , Triwiyono Andreas , Sulistyo Djoko , Suyitno S
Published: May 2021

This paper focuses on the effect of polypropylene (PP) fibers on the mechanical properties and thermal conductivity of fly ash-based geopolymer foams. Class C Fly ash (FA) was used as a binder material. A mixture of sodium silicate (SS) and sodium hydroxide (SH) was used as an alkaline activator of the geopolymer binder. The foams were prepared mechanically by mixing the foaming agent with distilled water at high pressure. The foams were added to the geopolymer admixture with volumes of 40% and 60%. A small dosage of PP was varied from 0%, 0.25%, and 0.50% by weight of fly ash (FA). The result showed that the strength of foamed geopolymer rises as the PP fiber content increases. The PP fiber was proven to increase the tensile strength of foamed geopolymer due to the ability of PP fiber to connect the crack and improve the tensile strength. The PP fiber amount in this study significantly affects the thermal conductivity of foamed geopolymer. However, the thermal conductivity in this study has the same properties as lightweight concrete and a little higher than gypsum board.
Ethical Considerations in Chemotherapy and Vaccines in Cancer Patients in Times of the COVID-19 Pandemic
Authors: Schiappacasse Guido V.
Published: May 2021

The COVID-19 situation is a worldwide health emergency with strong implications in clinical oncology. In this viewpoint, we address two crucial dilemmas from the ethical dimension: (1) Is it ethical to postpone or suspend cancer treatments which offer a statistically significant benefit in quality of life and survival in cancer patients during this time of pandemic?; (2) Should we vaccinate cancer patients against COVID-19 if scientific studies have not included this subgroup of patients? Regarding the first question, the best available evidence applied to the ethical principles of Beauchamp and Childress shows that treatments (such as chemotherapy) with clinical benefit are fair and beneficial. Indeed, the suspension or delay of such treatments should be considered malefic. Regarding the second question, applying the doctrine of double-effect, we show that the potential beneficial effect of vaccines in the population with cancer (or those one that has had cancer) is much higher than the potential adverse effects of these vaccines. In addition, there is no better and less harmful known solution.
Statistical Analysis and Neural Network in Detecting Steel Cord Failures in Conveyor Belts
Authors: Olchówka Dominika , Rzeszowska Aleksandra , Jurdziak Leszek , Błażej Ryszard
Published: May 2021

This paper presents the identification and classification of steel cord failures in the conveyor belt core based on an analysis of a two-dimensional image of magnetic field changes recorded using the Diagbelt system around scanned failures in the test belt. The obtained set of identified changes in images, obtained for numerous parameters settings of the device, were the base for statistical analysis. This analysis makes it possible to determine the Pearson’s linear correlation coefficient between the parameters being changed and the image of the failures. In the second stage of the research, artificial intelligence methods were applied to construct a multilayer neural network (MLP) and to teach it appropriate identification of damage. In both methods, the same data sets were used, which made it possible to compare methods.
Design and Testing of a Low-Tech DEW Generator for Determining Electromagnetic Immunity of Standard Electronic Circuits
Authors: Dražan Libor , Križan René , Popela Miroslav
Published: May 2021

This article describes the effect of high-power electromagnetic environments (HPEMs) on the operation of all basic elements of electrical power networks. Frequency bands are defined for the HPEM environments. Attention is focused particularly on directed energy weapons (DEWs) and intentional electromagnetic interference (IEMI). A classification of DEW and IEMI generators in terms of E-field level and target distance from the DEW or IEMI generator antenna aperture is also described. The main focus of this article is on the design and testing of a low-tech DEW generator used to determine the electromagnetic immunity of standard electronic circuits. In addition, verification of electromagnetic immunity for a simple electronic circuit without adequate protection against the E-field is also explained. The outcome of this article is the determination of the E-field limits for fault-free operation, for malfunctioning states of the tested circuits and for irreversible destruction of the circuits. The measured E-field was compared to basic microwave radiation theory and to simulation results in COMSOL Multiphysics software (COMSOL, Inc. 100 District Avenue Burlington, MA 01803 USA).
Assessment of the Radiotoxicity of Spent Nuclear Fuel from a Fleet of PWR Reactors
Authors: Oettingen Mikołaj
Published: May 2021

The paper presents the methodology for the estimation of the long-term actinides radiotoxicity and isotopic composition of spent nuclear fuel from a fleet of Pressurized Water Reactors (PWR). The methodology was developed using three independent numerical tools: the Spent Fuel Isotopic Composition database, the Nuclear Fuel Cycle Simulation System and the Monte Carlo Continuous Energy Burnup Code. The validation of spent fuel isotopic compositions obtained in the numerical modeling was performed using the available experimental data. A nuclear power embarking country benchmark was implemented for the verification and testing of the methodology. The obtained radiotoxicity reaches the reference levels at about 1.3 × 105 years, which is common for the PWR spent nuclear fuel. The presented methodology may be incorporated into a more versatile numerical tool for the modeling of hybrid energy systems.
SHP Assessment for a Run-of-River (RoR) Scheme Using a Rectangular Mesh Sweeping Approach (MSA) Based on GIS
Authors: Alcalá Gerardo , Grisales-Noreña Luis Fernando , Hernandez-Escobedo Quetzalcoatl , Muñoz-Criollo Jose Javier , Revuelta-Acosta J. D.
Published: May 2021

This work proposed a base method for automated assessment of Small Hydro-Power (SHP) potential for a run-of-river (RoR) scheme using geographic information systems (GIS). The hydro-power potential (HP) was represented through a comprehensive methodology consisting of a structured raster database. A calibrated and validated hydrological model (Soil and Water Assessment Tool—SWAT) was used to estimate monthly streamflow as the Mesh Sweeping Approach (MSA) driver. The methodology was applied for the upper part of the Huazuntlan River Watershed in Los Tuxtlas Mountains, Mexico. The MSA divided the study area into a rectangular mesh. Then, at every location within the mesh, SHP was obtained. The main components of the MSA as a RoR scheme were the intake, the powerhouse, and the surge tank. The surge tank was located at cells where the hydro-power was calculated and used as a reference to later locate the intake and powerhouse by maximizing the discharge and head. SHP calculation was performed by sweeping under different values of the penstock’s length, and the headrace’s length. The maximum permissible lengths for these two variables represented potential hydro-power generation locations. Results showed that the headrace’s length represented the major contribution for hydro-power potential estimation. Additionally, values of 2000 m and 1500 m for the penstock and the headrace were considered potential thresholds as there is no significant increment in hydro-power after increasing any of these values. The availability of hydro-power on a raster representation has advantages for further hydro-power data analysis and processing.
Effects of Time to Unactuate Air Conditioning on Fire Growth
Authors: Wang Teng-Yi , Tsai Kuang-Chung
Published: May 2021

Air conditioning systems have become essential equipment in many buildings. However, fire safety design and management in buildings rarely consider whether to turn the system off or keep it on in a fire. This study ignites a stack of wood in a room center or corner to explore the influence of air inlet actions of a fan coil unit (FCU) with the door opened or closed. Simulation results using Fire Dynamics Simulator (FDS) demonstrate that the heat release rate (HRR) and room temperature obviously decrease when the room doorway is closed, regardless of whether the air conditioner is turned on. The air supply for combustion is poor. When the door of the room is opened, turning off the air conditioner can effectively reduce the HRR and the room temperature in the early stages of fire growth. However, along with the fire growth, turning on air conditioning can help decrease the heat radiation feedback and the consequent HRR. Therefore, the conclusion that air conditioning always enhances a fire because it provides oxygen may not always be correct.
Experimental Study of Creep Acoustic Emission Characteristics of Coal Bodies around Boreholes under Different Moisture Contents
Authors: Zhang Tianjun , Ling Zhiqiang , Pang Mingkun , Meng Yukai
Published: May 2021

Water content is an important factor in the deformation-destruction process of coal bodies. To analyze the influence of water on the creep acoustic emission (AE) characteristics of coal rock surrounding a borehole, we conducted graded loading creep AE tests of single-hole specimens with different water contents (0%, 4%, 8% and water-saturation) under uniaxial loading. The findings include the following: the water content affects the creep mechanical properties of the coal body around a borehole. The creep transient strain and steady-state strain increased exponentially with rising water content; the saturated specimen showed the highest increase, reaching 44.5% and 28.6%, respectively. The specimen water content affected the cumulative ringing count (CRC) and the axial strain during creep. The axial strain increased with rising water content, the CRC increased linearly with rising axial strain. The higher the water content, the greater the CRC rise. At different stress levels, the CRC in the 4%, 8% and saturated water content specimens changed by 43%, 53% and 74%, respectively. The AE ringing rate showed a pattern of grow–decline–stabilize at each creep stage. The AEs decreased significantly with the rising water content and the creep curve lagged behind the AE data. This paper provides guidelines for gas extraction, borehole maintenance and AE detection.
Multiphase Multicomponent Numerical Modeling for Hydraulic Fracturing with N-Heptane for Efficient Stimulation in a Tight Gas Reservoir of Germany
Authors: Mehmood Faisal , Hou Michael , Liao Jianxing , Haris Muhammad , Cao Cheng , Luo Jiashun
Published: May 2021

Conventionally, high-pressure water-based fluids have been injected for hydraulic stimulation of unconventional petroleum resources such as tight gas reservoirs. Apart from improving productivity, water-based frac-fluids have caused environmental and technical issues. As a result, much of the interest has shifted towards alternative frac-fluids. In this regard, n-heptane, as an alternative frac-fluid, is proposed. It necessitates the development of a multi-phase and multi-component (MM) numerical simulator for hydraulic fracturing. Therefore fracture, MM fluid flow, and proppant transport models are implemented in a thermo-hydro-mechanical (THM) coupled FLAC3D-TMVOCMP framework. After verification, the model is applied to a real field case study for optimization of wellbore x in a tight gas reservoir using n-heptane as the frac-fluid. Sensitivity analysis is carried out to investigate the effect of important parameters, such as fluid viscosity, injection rate, reservoir permeability etc., on fracture geometry with the proposed fluid. The quicker fracture closure and flowback of n-heptane compared to water-based fluid is advantageous for better proppant placement, especially in the upper half of the fracture and the early start of natural gas production in tight reservoirs. Finally, fracture designs with a minimum dimensionless conductivity of 30 are proposed.
Maternal Economic Well-Being and Mental Health among Young Adult Children: Race/Ethnicity
Authors: Lee Jaewon
Published: May 2021

This study aimed to examine the relationship between maternal economic well-being and children’s mental health outcomes in adulthood and to consider the moderating effect of race/ethnicity. This study used data from the National Longitudinal Survey of Youth 1979 and the National Longitudinal Survey of Youth 79 for Children and Young Adults. The two datasets were merged, and 4224 pairs were selected for the final sample. Ordinary linear regression and logistic regression analyses were used. Poverty and lower net worth among mothers were positively associated with their children’s depression in young adulthood. Race/ethnicity moderated the relationship between maternal poverty and children’s depression. Therefore, women’s economic resources may be an important factor in the development of mental health issues among their children in young adulthood. Developing anti-poverty policies that target women may assist in reducing depressive symptoms in their children once they reach young adulthood, specifically for non-Hispanic White children.
Effect of Digestate and Straw Combined Application on Maintaining Rice Production and Paddy Environment
Authors: Hu Xue , Liu Hongyi , Xu Chengyu , Huang Xiaomin , Jiang Min , Zhuang Hengyang , Huang Lifen
Published: May 2021

Few studies have focused on the combined application of digestate and straw and its feasibility in rice production. Therefore, we conducted a two-year field experiment, including six treatments: without nutrients and straw (Control), digestate (D), digestate + fertilizer (DF), digestate + straw (DS), digestate + fertilizer + straw (DFS) and conventional fertilizer + straw (CS), to clarify the responses of rice growth and paddy soil nutrients to different straw and fertilizer combinations. Our results showed that digestate and straw combined application (i.e., treatment DFS) increased rice yield by 2.71 t ha−1 compared with the Control, and digestate combined with straw addition could distribute more nitrogen (N) to rice grains. Our results also showed that the straw decomposition rate at 0 cm depth under DS was 5% to 102% higher than that under CS. Activities of catalase, urease, sucrase and phosphatase at maturity under DS were all higher than that under both Control and CS. In addition, soil organic matter (SOM) and total nitrogen (TN) under DS and DFS were 20~26% and 11~12% higher than that under B and DF respectively, suggesting straw addition could benefit paddy soil quality. Moreover, coupling straw and digestate would contribute to decrease the N content in soil surface water. Overall, our results demonstrated that digestate and straw combined application could maintain rice production and have potential positive paddy environmental effects.
The pLysRS-Ap4A Pathway in Mast Cells Regulates the Switch from Host Defense to a Pathological State
Authors: Govindaraj Sharmila , Paruchuru Lakshmi Bhargavi , Razin Ehud
Published: May 2021

The innate and adaptive immune systems play an essential role in host defense against pathogens. Various signal transduction pathways monitor and balance the immune system since an imbalance may promote pathological states such as allergy, inflammation, and cancer. Mast cells have a central role in the regulation of the innate/adaptive immune system and are involved in the pathogenesis of many inflammatory and allergic diseases by releasing inflammatory mediators such as histamines, proteases, chemotactic factors, and cytokines. Although various signaling pathways are associated with mast cell activation, our discovery and characterization of the pLysRS-Ap4A signaling pathway in these cells provided an additional important step towards a full understanding of the intracellular mechanisms involved in mast cell activation. In the present review, we will discuss in depth this signaling pathway’s contribution to host defense and the pathological state.
Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy
Authors: Forró Timea , Bajkó Zoltán , Bălașa Adrian , Bălașa Rodica
Published: May 2021

Ischemic stroke is a damaging cerebral vascular disease associated with high disability and mortality rates worldwide. In spite of the continuous development of new diagnostic and prognostic methods, early detection and outcome prediction are often very difficult. The neurovascular unit (NVU) is a complex multicellular entity linking the interactions between neurons, glial cells, and brain vessels. Novel research has revealed that exosome-mediated transfer of microRNAs plays an important role in cell-to-cell communication and, thus, is integral in the multicellular crosstalk within the NVU. After a stroke, NVU homeostasis is altered, which induces the release of several potential biomarkers into the blood vessels. The addition of biological data representing all constituents of the NVU to clinical and neuroradiological findings can significantly advance stroke evaluation and prognosis. In this review, we present the current literature regarding the possible beneficial roles of exosomes derived from the components of the NVU and multipotent mesenchymal stem cells in preclinical studies of ischemic stroke. We also discuss the most relevant clinical trials on the diagnostic and prognostic roles of exosomes in stroke patients.
Spatio-Temporal Distribution of Cell Wall Components in the Placentas, Ovules and Female Gametophytes of Utricularia during Pollination
Authors: Płachno Bartosz Jan , Kapusta Małgorzata , Świątek Piotr , Banaś Krzysztof , Miranda Vitor F. O. , Bogucka-Kocka Anna
Published: May 2021

In most angiosperms, the female gametophyte is hidden in the mother tissues and the pollen tube enters the ovule via a micropylar canal. The mother tissues play an essential role in the pollen tube guidance. However, in Utricularia, the female gametophyte surpasses the entire micropylar canal and extends beyond the limit of the integument. The female gametophyte then invades the placenta and a part of the central cell has direct contact with the ovary chamber. To date, information about the role of the placenta and integument in pollen tube guidance in Utricularia, which have extra-ovular female gametophytes, has been lacking. The aim of this study was to evaluate the role of the placenta, central cell and integument in pollen tube pollen tube guidance in Utricularia nelumbifolia Gardner and Utricularia humboldtii R.H. Schomb. by studying the production of arabinogalactan proteins. It was also determined whether the production of the arabinogalactan proteins is dependent on pollination in Utricularia. In both of the examined species, arabinogalactan proteins (AGPs) were observed in the placenta (epidermis and nutritive tissue), ovule (integument, chalaza), and female gametophyte of both pollinated and unpollinated flowers, which means that the production of AGPs is independent of pollination; however, the production of some AGPs was lower after fertilization. There were some differences in the production of AGPs between the examined species. The occurrence of AGPs in the placental epidermis and nutritive tissue suggests that they function as an obturator. The production of some AGPs in the ovular tissues (nucellus, integument) was independent of the presence of a mature embryo sac.
Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43
Authors: Fukuyama Kouji , Okada Motohiro
Published: May 2021

Recently, accumulating preclinical findings suggest the possibility that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of schizophrenia and affective disorder. Therefore, to explore the novel mechanisms of mood-stabilizing effects associated with tripartite synaptic transmission, the present study determined the effects of mood-stabilizing antipsychotics, clozapine (CLZ), quetiapine (QTP) and brexpiprazole (BPZ), on the astroglial l-glutamate release and expression of connexin43 (Cx43) in the astroglial plasma membrane using cortical primary cultured astrocytes. Neither acute (for 120 min) nor subchronic (for 7 days) administrations of CLZ, QTP and BPZ affected basal astroglial l-glutamate release, whereas both acute and subchronic administration of CLZ, QTP and BPZ concentration-dependently enhanced astroglial l-glutamate release through activated hemichannels. Subchronic administration of therapeutic-relevant concentration of valproate (VPA), a histone deacetylase inhibiting mood-stabilizing antiepileptic drug, enhanced the stimulatory effects of therapeutic-relevant concentration of CLZ, QTP and BPZ on astroglial l-glutamate release through activated hemichannel. Subchronic administration of therapeutic-relevant concentration of CLZ, QTP and BPZ did not affect Cx43 protein expression in the plasma membrane during resting stage. After subchronic administration of VPA, acute and subchronic administration of therapeutic-relevant concentrations of CLZ increased Cx43 protein expression in the plasma membrane. Both acute administrations of therapeutic-relevant concentrations of QTP and BPZ did not affect, but subchronic administrations enhanced Cx43 protein expression in the astroglial plasma membrane. Furthermore, protein kinase B (Akt) inhibitor suppressed the stimulatory effects of CLZ and QTP, but did not affect Cx43 protein expression in the astroglial plasma membrane. These results suggest that three mood-stabilizing atypical antipsychotics, CLZ, QTP and BPZ enhance tripartite synaptic glutamatergic transmission due to enhancement of astroglial Cx43 containing hemichannel activities; however, the Cx43 activating mechanisms of these three mood-stabilizing antipsychotics were not identical. The enhanced astroglial glutamatergic transmission induced by CLZ, QTP and BPZ is, at least partially, involved in the actions of these three mood-stabilizing antipsychotics.
In Vitro Framework to Assess the Anti-Helicobacter pylori Potential of Lactic Acid Bacteria Secretions as Alternatives to Antibiotics
Authors: Whiteside Samantha A. , Mohiuddin Mahi M. , Shlimon Sargon , Chahal Jaspreet , MacPherson Chad W. , Jass Jana , Tompkins Thomas A. , Creuzenet Carole
Published: May 2021

Helicobacter pylori is a prevalent bacterium that can cause gastric ulcers and cancers. Lactic acid bacteria (LAB) ameliorate treatment outcomes against H. pylori, suggesting that they could be a source of bioactive molecules usable as alternatives to current antibiotics for which resistance is mounting. We developed an in vitro framework to compare the anti-H. pylori properties of 25 LAB and their secretions against H. pylori. All studies were done at acidic and neutralized pH, with or without urea to mimic various gastric compartments. Eighteen LAB strains secreted molecules that curtailed the growth of H. pylori and the activity was urea-resistant in five LAB. Several LAB supernatants also reduced the urease activity of H. pylori. Pre-treatment of H. pylori with acidic LAB supernatants abrogated its flagella-mediated motility and decreased its ability to elicit pro-inflammatory IL-8 cytokine from human gastric cells, without reverting the H. pylori-induced repression of other pro-inflammatory cytokines. This study identified the LAB that have the most anti-H. pylori effects, decreasing its viability, its production of virulence factors, its motility and/or its ability to elicit pro-inflammatory IL-8 from gastric cells. Once identified, these molecules can be used as alternatives or complements to current antibiotics to fight H. pylori infections.
Structure and Dynamics of Meprin β in Complex with a Hydroxamate-Based Inhibitor
Authors: Linnert Miriam , Fritz Claudia , Jäger Christian , Schlenzig Dagmar , Ramsbeck Daniel , Kleinschmidt Martin , Wermann Michael , Demuth Hans-Ulrich , Parthier Christoph , Schilling Stephan
Published: May 2021

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among these the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in orientation within the active site, the structural data as well as binding analyses, including molecular dynamics simulations, support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.
Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases
Authors: Bernatoniene Jurga , Kazlauskaite Jurga Andreja , Kopustinskiene Dalia Marija
Published: May 2021

Isoflavones are phytoestrogens of plant origin, mostly found in the members of the Fabaceae family, that exert beneficial effects in various degenerative disorders. Having high similarity to 17-β-estradiol, isoflavones can bind estrogen receptors, scavenge reactive oxygen species, activate various cellular signal transduction pathways and modulate growth and transcription factors, activities of enzymes, cytokines, and genes regulating cell proliferation and apoptosis. Due to their pleiotropic activities isoflavones might be considered as a natural alternative for the treatment of estrogen decrease-related conditions during menopause. This review will focus on the effects of isoflavones on inflammation and chronic degenerative diseases including cancer, metabolic, cardiovascular, neurodegenerative diseases, rheumatoid arthritis and adverse postmenopausal symptoms.
Treg-Resistant Cytotoxic CD4+ T Cells Dictate T Helper Cells in Their Vicinity: TH17 Skewing and Modulation of Proliferation
Authors: Hoeks Cindy , Vanheusden Marjan , Peeters Liesbet M. , Stinissen Piet , Broux Bieke , Hellings Niels
Published: May 2021

Cytotoxic CD4+ T cells (CD4 CTL) are terminally differentiated T helper cells that contribute to autoimmune diseases, such as multiple sclerosis. We developed a novel triple co-culture transwell assay to study mutual interactions between CD4 CTL, conventional TH cells, and regulatory T cells (Tregs) simultaneously. We show that, while CD4 CTL are resistant to suppression by Tregs in vitro, the conditioned medium of CD4 CTL accentuates the suppressive phenotype of Tregs by upregulating IL-10, Granzyme B, CTLA-4, and PD-1. We demonstrate that CD4 CTL conditioned medium skews memory TH cells to a TH17 phenotype, suggesting that the CD4 CTL induce bystander polarization. In our triple co-culture assay, the CD4 CTL secretome promotes the proliferation of TH cells, even in the presence of Tregs. However, when cell−cell contact is established between CD4 CTL and TH cells, the proliferation of TH cells is no longer increased and Treg-mediated suppression is restored. Taken together, our results suggest that when TH cells acquire cytotoxic properties, these Treg-resistant CD4 CTL affect the proliferation and phenotype of conventional TH cells in their vicinity. By creating such a pro-inflammatory microenvironment, CD4 CTL may favor their own persistence and expansion, and that of other potentially pathogenic TH cells, thereby contributing to pathogenic responses in autoimmune disorders.
Plant Transcription Factors Involved in Drought and Associated Stresses
Authors: Hrmova Maria , Hussain Syed Sarfraz
Published: May 2021

Transcription factors (TFs) play a significant role in signal transduction networks spanning the perception of a stress signal and the expression of corresponding stress-responsive genes. TFs are multi-functional proteins that may simultaneously control numerous pathways during stresses in plants—this makes them powerful tools for the manipulation of regulatory and stress-responsive pathways. In recent years, the structure-function relationships of numerous plant TFs involved in drought and associated stresses have been defined, which prompted devising practical strategies for engineering plants with enhanced stress tolerance. Vast data have emerged on purposely basic leucine zipper (bZIP), WRKY, homeodomain-leucine zipper (HD-Zip), myeloblastoma (MYB), drought-response elements binding proteins/C-repeat binding factor (DREB/CBF), shine (SHN), and wax production-like (WXPL) TFs that reflect the understanding of their 3D structure and how the structure relates to function. Consequently, this information is useful in the tailored design of variant TFs that enhances our understanding of their functional states, such as oligomerization, post-translational modification patterns, protein-protein interactions, and their abilities to recognize downstream target DNA sequences. Here, we report on the progress of TFs based on their interaction pathway participation in stress-responsive networks, and pinpoint strategies and applications for crops and the impact of these strategies for improving plant stress tolerance.
ABE8e with Polycistronic tRNA-gRNA Expression Cassette Sig-Nificantly Improves Adenine Base Editing Efficiency in Nicotiana benthamiana
Authors: Wang Zupeng , Liu Xiaoying , Xie Xiaodong , Deng Lei , Zheng Hao , Pan Hui , Li Dawei , Li Li , Zhong Caihong
Published: May 2021

Adenine base editor containing TadA8e (ABE8e) has been reported in rice. However, the application of ABE8e in other plant species has not been described, and the comparison between ABE8e and ABE7.10, which is widely used in plants, has also been poorly studied. Here, we developed the ABE8e with the polycistronic tRNA-gRNA expression cassette (PTG-ABE8e) and PTG-ABE7.10 and compared their A-to-G editing efficiencies using both transient and stable transformation in the allotetraploid Nicotiana benthamiana. We found that the editing efficiency of PTG-ABE8e was significantly higher than that of PTG-ABE7.10, indicating that ABE8e was more efficient for A-to-G conversion in N. benthamiana. We further optimized the ABE8e editing efficiency by changing the sgRNA expression cassette and demonstrated that both PTG and single transcript unit (STU) enhanced ABE8e efficiency for A-to-G conversion in N. benthamiana. We also estimated the potential off-target effect of PTG-ABE8e at potential off-targeting sites predicted using an online tool in transgenic plants, and no off-target editing event was found for potential off-targeting sites selected, indicating that ABE8e could specifically facilitate A-to-G conversion. Our results showed that ABE8e with PTG structure was more suitable for A-to-G conversion in N. benthamiana and provided valuable clues for optimizing ABE tools in other plants.
Advances and Perspectives in Tissue Culture and Genetic Engineering of Cannabis
Authors: Hesami Mohsen , Baiton Austin , Alizadeh Milad , Pepe Marco , Torkamaneh Davoud , Jones Andrew Maxwell Phineas
Published: May 2021

For a long time, Cannabis sativa has been used for therapeutic and industrial purposes. Due to its increasing demand in medicine, recreation, and industry, there is a dire need to apply new biotechnological tools to introduce new genotypes with desirable traits and enhanced secondary metabolite production. Micropropagation, conservation, cell suspension culture, hairy root culture, polyploidy manipulation, and Agrobacterium-mediated gene transformation have been studied and used in cannabis. However, some obstacles such as the low rate of transgenic plant regeneration and low efficiency of secondary metabolite production in hairy root culture and cell suspension culture have restricted the application of these approaches in cannabis. In the current review, in vitro culture and genetic engineering methods in cannabis along with other promising techniques such as morphogenic genes, new computational approaches, clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR/Cas9-equipped Agrobacterium-mediated genome editing, and hairy root culture, that can help improve gene transformation and plant regeneration, as well as enhance secondary metabolite production, have been highlighted and discussed.
DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy
Authors: Chen Jinglong , Wang Danping , Zong Yibo , Yang Xiaojing
Published: May 2021

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.
Ceramide and Related Molecules in Viral Infections
Authors: Beckmann Nadine , Becker Katrin Anne
Published: May 2021

Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.
Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment
Authors: Zhan Chenyang , Prabhu Vinay , Kang Stella K. , Li Clayton , Zhu Yuli , Kim Sooah , Olsen Sonja , Jacobson Ira M. , Dagher Nabil N. , Carney Brendan , Hickey Ryan M. , Taslakian Bedros
Published: May 2021

Background: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. Methods: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6–9 months) and late follow-up (9–16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. Results: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. Conclusion: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.
High AC and DC Electroconductivity of Scalable and Economic Graphite–Diamond Polylactide Nanocomposites
Authors: Fal Jacek , Bulanda Katarzyna , Oleksy Mariusz , Sobczak Jolanta , Shi Jinwen , Liu Maochang , Boncel Sławomir , Żyła Gaweł
Published: May 2021

Two types of graphite/diamond (GD) particles with different ash content was applied to prepare new electroconductive polylactide (PLA)-based nanocomposites. Four samples of nanocomposites for each type of GD particles with mass fraction 0.01, 0.05, 0.10, and 0.15 were prepared via an easily scalable method—melt blending. The samples were subjected to the studies of electrical properties via broadband dielectric spectroscopy. The results indicated up to eight orders of magnitude improvement in the electrical conductivity and electrical permittivity of the most loaded nanocomposites, in reference to the neat PLA. Additionally, the influence of ash content on the electrical conductivity of the nanocomposites revealed that technologically less-demanding fillers, i.e., of higher ash content, were the most beneficial in the light of nanofiller dispersibility and the final properties.