bluuebunny/crossref_metadata_2025 huggingface dataset:
Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children
Authors: Nguyen Huong Thi Thu , Vu Dung Chi , Nguyen Duc Minh , Dang Quang Dinh , Tran Van Khanh , Le Hung , Tong Son Minh
Published: April 2021

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass, caused mainly by mutations in collagen type I encoding genes. The current study aimed to evaluate dentinogenesis imperfecta (DI), oral manifestations and caries status of OI children. Sixty-eight children (41 males, 27 females) aged from 3 to 17 years old (mean 9 ± 4.13) participated in the study. Participants were classified into three OI type groups (I—2 cases, III—31 cases and IV—35 cases). Clinical examination and an orthopantomogram were used to obtain prevalences and associations of DI, caries status, malocclusion, crossbite, open bite, eruption, impaction and missing teeth with OI. The prevalence of DI among OI patients was 47.1%, more common in OI type III than type IV. The yellow-brown discoloration type was more vulnerable to attrition than the opalescent-grey one in the primary dentition. OI seemed not to have a high risk of caries; the prevalence of caries was 69.1%. A high incidence of malocclusion, crossbite and open bite was observed. In-depth oral information would provide valuable data for better dental management in OI patients. Parents and general doctors should pay more attention to dental care to prevent caries and premature tooth loss.
Advances in Atomtronics
Authors: Pepino Ron A.
Published: April 2021

Atomtronics is a relatively new subfield of atomic physics that aims to realize the device behavior of electronic components in ultracold atom-optical systems. The fact that these systems are coherent makes them particularly interesting since, in addition to current, one can impart quantum states onto the current carriers themselves or perhaps perform quantum computational operations on them. After reviewing the fundamental ideas of this subfield, we report on the theoretical and experimental progress made towards developing externally-driven and closed loop devices. The functionality and potential applications for these atom analogs to electronic and spintronic systems is also discussed.
Comparative Economics of Conventional, Organic, and Alternative Agricultural Production Systems
Authors: Durham Timothy C. , Mizik Tamás
Published: April 2021

Agricultural production systems are a composite of philosophy, adoptability, and careful analysis of risks and rewards. The two dominant typologies include conventional and organics, while biotechnology (GM) and Integrated Pest Management (IPM) represent situational modifiers. We conducted a systematic review to weigh the economic merits—as well as intangibles through an economic lens—of each standalone system and system plus modifier, where applicable. Overall, 17,485 articles were found between ScienceDirect and Google Scholar, with 213 initially screened based on putative relevance. Of those, 82 were selected for an in-depth analysis, with 63 ultimately used. Economically, organic generally outperformed conventional systems. This is largely due to their lower production costs and higher market price. However, organic farms face lower yields, especially in the fruit, vegetable, and animal husbandry sectors. With that said, organic farming can provide significant local environmental benefits. Integrated pest management (IPM) is a potentiator of either core system. As a risk reduction and decision-making framework, it is labor intensive. However, this can be offset by input reductions without yield penalty compared to a conventional baseline. Biotechnology is a rapidly emerging production system, notably in developing countries. The use of GM crops results in lower production cost and higher yields. As a conventional modifier, its major advantage is scale-neutrality. Thus, smaller and lower income farmers may achieve higher gross margin. The main source of environmental benefits is reduced pesticide use, which implies a decreased need for fuel and labor. Barring external influences such as subsidies and participation in prescriptive labeling programs, farmers should focus on an a la carte approach (as opposed to discrete system adoption) to optimize their respective enterprises.
Collective Action Problems and Direct Democracy: An Analysis of Georgia’s 2010 Trauma Care Funding Amendment
Authors: Hall Joshua C. , Horpedahl Jeremy , Stephenson E. Frank
Published: April 2021

In 2010, Georgians voted on a proposed constitutional amendment that would have increased motor vehicle licensing fees by USD 10 with the proceeds dedicated to maintaining and expanding the state’s trauma care centers. This paper examines voter support for the referendum across counties and finds (1) that counties located near trauma centers in neighboring states had significantly lower support for the amendment and (2) that counties already having trauma centers had higher support for the amendment. These results are, respectively, consistent with free-riding and rent-seeking on the part of voters.
Electrolytic Reduction of Titanium Dioxide in Molten LiCl–Li2O
Authors: Shi Meng , Liu Bin , Li Shelly , Zhao Haiyan
Published: April 2021

The electrolytic reduction of TiO2 in LiCl–Li2O (1 wt.%) at 650 °C was investigated under a series of cathodic reduction potentials and applied charges to provide a mechanistic understanding of the electrochemical characteristics of the system. The optimal cathodic reduction potential was determined as being −0.3 V vs. Li/Li+. Li2TiO3 and LiTiO2 were structurally identified as intermediate and partial reduction products of the TiO2 electrolytic reduction. The reduction of LiTiO2 was extremely slow and reversible due to its high stability and the detrimental effect of Li2O accumulation within the solid particles. The most reduced product obtained in this study was LiTiO2, which was achieved when using 150% of the theoretical charge under the optimal reduction potential. The highest reduction extent obtained in this study was 25%. Based on theoretical DFT modeling, a detailed multistep reduction mechanism and scheme were proposed for TiO2 electrolytic reduction in LiCl–Li2O (1 wt.%) at 650 °C.
Analytical Model of an Induction Motor Taking into Account the Punching Process Influence on the Material Properties’ Change of Lamination
Authors: Dems Maria , Gmyrek Zbigniew , Komeza Krzysztof
Published: April 2021

The technologies of cutting the cores of electric machines change the magnetic properties and the loss of the electrical sheets used, affecting the machine’s parameters, mainly power losses and efficiency. This is particularly important in the case of induction motors, which are a significant consumer of electricity. Therefore, the problem of increasing their efficiency is important from the point of view of environmental impact. The article presents a method of approximating a material’s magnetic properties based on the results of measurements carried out with specimens of various widths. The presented method allows for an approximate representation of the changes in the structure of the material caused by the cutting technology. It is used in the analytical method for calculating motor parameters, and gives results that are in good agreement with the measurement. This method can determine the operating parameters of electrical machines of various sizes and rated powers.
Analysis of the Magnetohydrodynamic Behavior of the Fully Developed Flow of Conducting Fluid
Authors: Fonseca Wellington da Silva , Araújo Ramon C. F. , Silva Marcelo de Oliveira e , Cruz Daniel Onofre de A.
Published: April 2021

Important industrial applications are based on magnetohydrodynamics (MHD), which concerns the flow of electrically conducting fluids immersed in external magnetic fields. Using the Finite Volume Method, we performed a 3D numerical study of the MHD flow of a conducting fluid in a circular duct. The flow considered was laminar and fully developed. Along the initial section of the duct, there were magnets placed around the duct producing magnetic fields in the radial direction. Two arrangements of magnetic field orientation were considered: fields pointing toward and away from the duct’s center alternately, and all fields pointing toward the duct’s center. For each arrangement of magnets, various intensities of magnetic fields were considered to evaluate two effects: the influence of the magnetic field on the flow velocity, and the influence of the flow velocity on magnetic field induction. It was found that for the second arrangement of magnets and Hartmann numbers larger than 10, the flow velocity was reduced by as much as 35%, and the axial magnetic induction was as high as the field intensity applied by each magnet. Those effects were negligible for the first arrangement and low fields because of the distribution of field lines inside the duct for these situations.
Nuclear Power Risk Perception in Serbia: Fear of Exposure to Radiation vs. Social Benefits
Authors: Cvetković Vladimir M. , Öcal Adem , Lyamzina Yuliya , Noji Eric K. , Nikolić Neda , Milošević Goran
Published: April 2021

Nuclear power remains one of the most accessible choices in addressing environmental and social concerns due to the continuously increasing energy needs around the world. While it remains an excellent source of energy due to its low price and low level of emissions, potential accidents remain a serious problem. An example of such is the most recent accident in the Fukushima Daiichi Nuclear Power Plant (2011), which reminded the world of the potential risks of nuclear energy and the consequences of which continue to have a lasting effect. There is no nuclear power plant in Serbia, but there are about 15 nuclear power stations scattered within its neighboring countries. Therefore, the Serbian Government decided to study how the Serbian public perceives the risks related to the potential construction of nuclear power stations in the country, nuclear energy in general, and its possible benefits and risks. The objective of this paper is to present the results of this assessment along with a literature overview on the (environmental) risk of nuclear power. A pilot study consisted of a series of 270 randomized face-to-face interviews that took place in the public square of Belgrade in March 2019. Logistic regression was used to examine the cumulative effects of the different risk factors. The results showed that the majority of the respondents are skeptical and do not support the construction of nuclear power stations in Serbia. Furthermore, this research identified several additional important correlations that have a significant impact on the public perception of risk.
Performance Study and Optimization Design of High-Speed Amorphous Alloy Induction Motor
Authors: Fan Zeyang , Yi Hong , Xu Jian , Xie Kun , Qi Yue , Ren Sailin , Wang Hongdong
Published: April 2021

Due to the simple structure, low inertia and the ability to operate for a long time under high-speed and high-temperature conditions, the induction motor is widely used in high-speed applications. Aiming at the most prominent loss and stress problems in high-speed induction motors, the use of low loss material and the choice of a reliable rotor structure are effective optimized methods. In this paper, the electromagnetic loss, stator temperature distribution and performance parameters of high-speed induction motor are analyzed with stator cores of different materials. In addition, for the different rotor structures, the mechanical stress is compared. Furthermore, the comparison and analysis are used to improve the motor performance and provide a reference for prototype development. A performance test of the prototype is conducted, which proves the validity of the study in this paper.
Life-Cycle Assessment of a Rural Terraced House: A Struggle with Sustainability of Building Renovations
Authors: Struhala Karel , Ostrý Milan
Published: April 2021

Contemporary research stresses the need to reduce mankind’s environmental impacts and achieve sustainability. One of the keys to this is the construction sector. New buildings have to comply with strict limits regarding resource consumption (energy, water use, etc.). However, they make up only a fraction of the existing building stock. Renovations of existing buildings are therefore essential for the reduction of the environmental impacts in the construction sector. This paper illustrates the situation using a case study of a rural terraced house in a village near Brno, Czech Republic. It compares the life-cycle assessment (LCA) of the original house and its proposed renovation as well as demolition followed by new construction. The LCA covers both the initial embodied environmental impacts (EEIs) and the 60-year operation of the house with several variants of energy sources. The results show that the proposed renovation would reduce overall environmental impacts (OEIs) of the house by up to 90% and the demolition and new construction by up to 93% depending on the selected energy sources. As such, the results confirm the importance of renovations and the installation of environmentally-friendly energy sources for achieving sustainability in the construction sector. They also show the desirability of the replacement of inefficient old buildings by new construction in specific cases.
The Impact of the Geometry of the Effective Propped Volume on the Economic Performance of Shale Gas Well Production
Authors: Soage Andres , Juanes Ruben , Colominas Ignasi , Cueto-Felgueroso Luis
Published: April 2021

We analyze the effect that the geometry of the Effective Propped Volume (EPV) has on the economic performance of hydrofractured multistage shale gas wells. We study the sensitivity of gas production to the EPV’s geometry and we compare it with the sensitivity to other parameters whose relevance in the production of shale gas is well known: porosity, kerogen content and permeability induced in the Stimulated Recovery Volume (SRV). To understand these sensitivities, we develop a high-fidelity 3D numerical model of shale gas flow that allows determining both the Estimated Ultimate Recovery (EUR) of gas as well as analyzing the decline curves of gas production (DCA). We find that the geometry of the EPV plays an important role in the economic performance and gas production of shale wells. The relative contribution of EPV geometry is comparable to that of induced permeability of the SRV or formation porosity. Our results may lead to interesting technological developments in the oild and gas industry that improve economic efficiency in shale gas production.
Diagnostic Row Reasoning Method Based on Multiple-Valued Evaluation of Residuals and Elementary Symptoms Sequence
Authors: Kościelny Jan Maciej , Syfert Michał , Wnuk Paweł
Published: April 2021

The paper analyses the research problem of conducting diagnostic reasoning for dynamic objects to eliminate the possibility of formulating false diagnoses resulting from different delays of the symptoms related to a particular fault while simultaneously striving to obtain high distinguishability. The research aimed to develop a new diagnostic inference method robust to symptom delays and characterised by high accuracy of generated diagnosis. Known methods ensuring the correctness of inference in the case of symptom delays but at the cost of reducing distinguishability of faults have been characterised. A new inference method was developed, which uses the three-valued residual evaluation and knowledge regarding elementary symptom sequences. A formal description of the diagnosing system and the proposed method are given. The method of obtaining the knowledge about the order of symptoms based on a cause-and-effect graph and was characterised. The method’s effectiveness was presented in simulation studies on the example of diagnosing a set of serially connected tanks. The comparison of the fault distinguishability obtained using the proposed method and other approaches illustrates the new method’s advantages.
Optimization Method for Operation Schedule of Microgrids Considering Uncertainty in Available Data
Authors: Takano Hirotaka , Goto Ryota , Hayashi Ryosuke , Asano Hiroshi
Published: April 2021

Operation scheduling in electric power grids is one of the most practical optimization problems as it sets a target for the efficient management of the electric power supply and demand. Advancement of a method to solve this issue is crucially required, especially in microgrids. This is because the operational capability of microgrids is generally lower than that of conventional bulk power grids, and therefore, it is extremely important to develop an appropriate, coordinated operation schedule of the microgrid components. Although various techniques have been developed to solve the problem, there is no established solution. The authors propose a problem framework and a solution method that finds the optimal operation schedule of the microgrid components considering the uncertainty in the available data. In the authors’ proposal, the objective function of the target problem is formulated as the expected cost of the microgrid’s operations. Since the risk of imbalance in the power supply and demand is evaluated as a part of the objective function, the necessary operational reserve power is automatically calculated. The usefulness of the proposed problem framework and its solution method was verified through numerical simulations and the results are discussed.
The Management of Environmental Resources in the Construction Sector: An Empirical Model
Authors: Vasilca Ionel-Sorinel , Nen Madlena , Chivu Oana , Radu Valentin , Simion Cezar-Petre , Marinescu Nicolae
Published: April 2021

This research emphasizes the analysis and assessment of the environmental impact in the construction sector. It aims to propose a model for analyzing the management of environmental resources in the building process. This specific sector presents a significant potential risk of negatively affecting the environment, through pollution, energy consumption, and waste generation. Environmental responsibility involves analyzing the environmental impact and implementing effective solutions for an adequate governance of the environmental resources. Various life cycle assessment methods are employed to design a new model of management of environmental resources, starting from the factors impacting the environment. The resulting model takes these factors into account and carries several advantages from an organizational point of view. One novel result is that the model can be applied at a microeconomic level as well as at a macroeconomic level. By implementing this model, the preconditions for reconfiguring operational conditions and processes with significant impact on resource consumption within construction projects can be created at a company level. As such, the objective for the construction sector is to manage the use of resources efficiently and, at the same time, to restore the areas possibly affected by the specific operations.
Porcelain Enamel Coatings
Authors: Russo Francesca , Rossi Stefano , Compagnoni Attilio Monzio
Published: April 2021

Porcelain enamel is an inorganic-type coating, which is applied to metals or glass for both decorative and functional purposes. This coating is a silica-based solidified glass mass obtained by high-temperature firing (temperature can range between 450 and 1200 °C depending on the substrate). Porcelain enamel coatings differ from ceramic coatings mainly by their glass structure and dilatation coefficient, and from organic paints mainly by the inorganic nature of the matrix and the chemical bond that exists between the coating and the substrate.
Prediction of Ecosystem Service Function of Grain for Green Project Based on Ensemble Learning
Authors: Li Huijie , Niu Xiang , Wang Bing
Published: April 2021

The Grain for Green Project (GGP) was implemented over 20 years ago as one of six major forestry projects in China, and its scope of implementation is still expanding. However, it is still unclear how many ecosystem services (ESs) the project will produce in the future. The GGP’s large-scale ecological monitoring officially started in 2015 and there is a lack of early monitoring data, making it challenging to predict the future ecological benefits. Therefore, this paper proposes a method to predict future ESs by using ecological monitoring data. First, a new ensemble learning system, auto-XGBoost-ET-DT, is developed based on ensemble learning theory. Using the GGP’s known ESs in 2015, 2017, and 2019, the missing ESs of the past decade have been evaluated via reverse regression. Data from 2020 to 2022 within a convolution neural network and the coupling coordination degree model have been used to analyze the coupling between the prediction results and economic development. The results show that the growth distributions of ESs in three years were as follows: soil consolidation, 3.70–6.34%; forest nutrient retention, 2.72–.71%; water conservation, 2.52–6.09%; carbon fixation and oxygen release, 3.00–4.64%; and dust retention, 3.82–5.75%. The coupling coordination degree of the ESs and economic development has been improved in 97% of counties in 2020 compared with 2019. The results verify a feasible ES prediction method and provide a basis for the progressive implementation of the GGP.
Quality, Bioactive Compounds, Antioxidant Capacity, and Enzymes of Raspberries at Different Maturity Stages, Effects of Organic vs. Conventional Fertilization
Authors: Frías-Moreno María Noemí , Parra-Quezada Rafael A. , González-Aguilar Gustavo , Ruíz-Canizales Jacqueline , Molina-Corral Francisco Javier , Sepulveda David R. , Salas-Salazar Nora , Olivas Guadalupe I.
Published: April 2021

Raspberries are important sources of bioactive compounds, whose synthesis is influenced by the fertilization system and the maturity stage. This study evaluated the effect of organic and conventional fertilization systems on raspberries at three maturity stages, pink, ripe, and overripe. Physicochemical characteristics, bioactive compounds (phenolic profile, vitamin C), antioxidant capacity (DPPH, FRAP, TEAC, and ORAC), phenolic-associated enzyme, phenylalanine ammonia lyase (PAL), and antioxidant enzymes (SOD, CAT, GPx, and APX) were evaluated. The physicochemical determination of the fruit did not reveal differences between fertilization systems. Regarding bioactive compounds, higher content of anthocyanins was found in organic raspberries at all maturity stages. Organic fertilization increased the content of ellagic acid and gallic acid at all stages of maturity. Higher content of caffeic, hydroxybenzoic, protocatechuic acid, and vitamin C was observed in organic raspberry at the overripe stage. Raspberries grown with organic fertilization exhibited higher values of antioxidant capacity by the DPPH, FRAP, and TEAC methods at all maturity stages. Raspberries under organic fertilization showed significantly greater activity of CAT, SOD, APX, GPX, and PAL. The present study suggests that organic fertilization induces oxidative stress causing an increase in antioxidant defense mechanisms, enhancing bioactive compound production, and improving antioxidant capacity in raspberries.
High-Pressure Processing for the Production of Added-Value Claw Meat from Edible Crab (Cancer pagurus)
Authors: Lian Federico , De Conto Enrico , Del Grippo Vincenzo , Harrison Sabine M. , Fagan John , Lyng James G. , Brunton Nigel P.
Published: April 2021

High-pressure processing (HPP) in a large-scale industrial unit was explored as a means for producing added-value claw meat products from edible crab (Cancer pagurus). Quality attributes were comparatively evaluated on the meat extracted from pressurized (300 MPa/2 min, 300 MPa/4 min, 500 MPa/2 min) or cooked (92 °C/15 min) chelipeds (i.e., the limb bearing the claw), before and after a thermal in-pack pasteurization (F9010 = 10). Satisfactory meat detachment from the shell was achieved due to HPP-induced cold protein denaturation. Compared to cooked or cooked–pasteurized counterparts, pressurized claws showed significantly higher yield (p < 0.05), which was possibly related to higher intra-myofibrillar water as evidenced by relaxometry data, together with lower volatile nitrogen levels. The polyunsaturated fatty acids content was unaffected, whereas the inactivation of total viable psychrotrophic and mesophilic bacteria increased with treatment pressure and time (1.1–1.9 log10 CFU g−1). Notably, pressurization at 300 MPa for 4 min resulted in meat with no discolorations and, after pasteurization, with high color similarity (ΔE* = 1.2–1.9) to conventionally thermally processed samples. Following further investigations into eating quality and microbiological stability, these HPP conditions could be exploited for producing uncooked ready-to-heat or pasteurized ready-to-eat claw meat products from edible crab.
Frequency and Time Dependence of Linear Polarization in Turbulent Jets of Blazars
Authors: Marscher Alan P. , Jorstad Svetlana G.
Published: April 2021

Time-variable polarization is an extremely valuable observational tool to probe the dynamical physical conditions of blazar jets. Since 2008, we have been monitoring the flux and linear polarization of a sample of gamma-ray bright blazars at optical frequencies. Some of the observations were performed on nightly or intra-night time-scales in four optical bands, providing information on the frequency and time dependence of the polarization. The observed behavior is similar to that found in simulations of turbulent plasma in a relativistic jet that contains a standing shock and/or a helical background magnetic field. Similar simulations predict the characteristics of X-ray synchrotron polarization of blazars that will be measured in the future by the Imaging X-ray Polarimetry Explorer (IXPE).
Development of a Motility Frailty Index in Patients with Gastroparesis
Authors: Winston Jared , Guzman Rojas Patricia , Stocker Abigail , Mathur Prateek , Lorenz Douglas , Daniels Michael , Abell Thomas
Published: April 2021

Introduction: Patients with symptoms (Sx) of gastrointestinal (GI) motor disorders have limitations in physical strength and mobility. We hypothesized that physical frailty correlated with severity of GI symptoms, and that a motility frailty index (MFI) could be constructed. Patients: We conducted a prospective pilot study on 40 patients, (38 F, 2 M, mean age 39.9 years) with the following diagnoses: 10 with diabetes mellitus and 30 with non-diabetic/idiopathic disorders. Upper and lower GI Sx were quantified using an FDA-compliant, traditional patient-reported outcomes (PRO) system. Methods: Patients underwent a series of physical performance measures involving standing balance (SB), usual walk speed (UW), and chair sit-and-stands (CS). A GI motility frailty index (MFI) was constructed by fitting several models with a combination of physical performance measures and correlating with PRO. Pearson’s correlation compared the constructed index with the GI Sx PRO to construct a GI MFI. Results: The studied patients collectively showed marked limitations in mobility compared with standard performance values with mean (sd) ratios of SB = 0.87 (0.20), UW = 0.45 (0.13), and CS = 0.38 (0.17). Correlations between physical mobility and GI Sx were noted for upper GI Sx (rho = 0.47, p = 0.002) but not for lower GI Sx. Conclusions: In this pilot study of patients with GI motility disorders, we found increased physical limitations on performance-based testing, which had a statistically significant positive correlation with severity of upper GI motor Sx using a standardized PRO system. A motility frailty index has been constructed that may serve as a basis for better quantifying limitations in patient mobility.
Research on Public Fitness Equipment Experience Based on Satisfaction
Authors: Zheng Zufang , Mo Jiancheng , Xu Yuanyuan
Published: April 2021

In order to improve the user experience of public fitness equipment, based on the principles of experience design principle, the Norman 3-level theory is used to obtain product materials, using safety, equipment practicality, product interest, and humanistic construction experience. The 5-level Likert evaluation scale is used to conduct a satisfaction survey on the index factors. According to the score, the fuzzy comprehensive evaluation method is applied to calculate the weights and average satisfaction values of the first and second indexes and discover the practical characteristics, interesting characteristics, and humanities of users. The characteristic satisfaction is low. The IPA model is used to analyze and evaluate the position of each evaluation index factor quadrant, and the experience factors that need improvement are obtained. In view of the analysis results, suggestions for advancement of public fitness equipment and factors in urgent need of improvement are put forward, and the safety experience refine design of the stroller is provided, which offers an effective reference for the experience design of public fitness equipment.
PIMS-TS, the New Paediatric Systemic Inflammatory Disease Related to Previous Exposure to SARS-CoV-2 Infection—“Rheumatic Fever” of the 21st Century?
Authors: Opoka-Winiarska Violetta , Grywalska Ewelina , Roliński Jacek
Published: April 2021

Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting that the experiences with ARF can be used in the management of patients with PIMS-TS. The aim of the article is to analyse the current data on PIMS-TS in relation to ARF. PIMS-TS and ARF are associated with an abnormal immune response to specific pathogens (SARS-CoV-2 and group A streptococcus, respectively). The main symptoms of both diseases are fever and cardiac involvement. Current therapy for PIMS-TS is based on anti-inflammatory treatment: intravenous immunoglobulin (first-line), intravenous glucocorticoids (second-line), or biological therapy (third-line; including interleukin [IL]-1 antagonists, IL-6 receptor blockers, and anti-tumour necrosis factor agents). Vaccination might be good prophylaxis, but the efficacy and safety of the vaccines against SARS-CoV-2 have not yet been established in children. Interesting insights may be gained by considering PIMS-TS in light of what is known of ARF due to their similar courses, but there are still many unanswered questions surrounding this disease and its pathogenesis.
Comparative Transcriptome Analysis Identified Candidate Genes for Late Leaf Spot Resistance and Cause of Defoliation in Groundnut
Authors: Gangurde Sunil S. , Nayak Spurthi N. , Joshi Pushpesh , Purohit Shilp , Sudini Hari K. , Chitikineni Annapurna , Hong Yanbin , Guo Baozhu , Chen Xiaoping , Pandey Manish K. , Varshney Rajeev K.
Published: April 2021

Late leaf spot (LLS) caused by fungus Nothopassalora personata in groundnut is responsible for up to 50% yield loss. To dissect the complex nature of LLS resistance, comparative transcriptome analysis was performed using resistant (GPBD 4), susceptible (TAG 24) and a resistant introgression line (ICGV 13208) and identified a total of 12,164 and 9954 DEGs (differentially expressed genes) respectively in A- and B-subgenomes of tetraploid groundnut. There were 135 and 136 unique pathways triggered in A- and B-subgenomes, respectively, upon N. personata infection. Highly upregulated putative disease resistance genes, an RPP-13 like (Aradu.P20JR) and a NBS-LRR (Aradu.Z87JB) were identified on chromosome A02 and A03, respectively, for LLS resistance. Mildew resistance Locus (MLOs)-like proteins, heavy metal transport proteins, and ubiquitin protein ligase showed trend of upregulation in susceptible genotypes, while tetratricopeptide repeats (TPR), pentatricopeptide repeat (PPR), chitinases, glutathione S-transferases, purple acid phosphatases showed upregulation in resistant genotypes. However, the highly expressed ethylene responsive factor (ERF) and ethylene responsive nuclear protein (ERF2), and early responsive dehydration gene (ERD) might be related to the possible causes of defoliation in susceptible genotypes. The identified disease resistance genes can be deployed in genomics-assisted breeding for development of LLS resistant cultivars to reduce the yield loss in groundnut.
Methods for Identifying Microbial Natural Product Compounds that Target Kinetoplastid RNA Structural Motifs by Homology and De Novo Modeled 18S rRNA
Authors: Mwangi Harrison Ndung’u , Muge Edward Kirwa , Wagacha Peter Waiganjo , Ndakala Albert , Mulaa Francis Jackim
Published: April 2021

The development of novel anti-infectives against Kinetoplastids pathogens targeting proteins is a big problem occasioned by the antigenic variation in these parasites. This is also a global concern due to the zoonosis of these parasites, as they infect both humans and animals. Therefore, we need not only to create novel antibiotics, but also to speed up the development pipeline for these antibiotics. This may be achieved by using novel drug targets for Kinetoplastids drug discovery. In this study, we focused our attention on motifs of rRNA molecules that have been created using homology modeling. The RNA is the most ambiguous biopolymer in the kinetoplatid, which carries many different functions. For instance, tRNAs, rRNAs, and mRNAs are essential for gene expression both in the pro-and eukaryotes. However, all these types of RNAs have sequences with unique 3D structures that are specific for kinetoplastids only and can be used to shut down essential biochemical processes in kinetoplastids only. All these features make RNA very potent targets for antibacterial drug development. Here, we combine in silico methods combined with both computational biology and structure prediction tools to address our hypothesis. In this study, we outline a systematic approach for identifying kinetoplastid rRNA-ligand interactions and, more specifically, techniques that can be used to identify small molecules that target particular RNA. The high-resolution optimized model structures of these kineoplastids were generated using RNA 123, where all the stereochemical conflicts were solved and energies minimized to attain the best biological qualities. The high-resolution optimized model’s structures of these kinetoplastids were generated using RNA 123 where all the stereochemical conflicts were solved and energies minimized to attain the best biological qualities. These models were further analyzed to give their docking assessment reliability. Docking strategies, virtual screening, and fishing approaches successfully recognized novel and myriad macromolecular targets for the myxobacterial natural products with high binding affinities to exploit the unmet therapeutic needs. We demonstrate a sensible exploitation of virtual screening strategies to 18S rRNA using natural products interfaced with classical maximization of their efficacy in phamacognosy strategies that are well established. Integration of these virtual screening strategies in natural products chemistry and biochemistry research will spur the development of potential interventions to these tropical neglected diseases.
The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment
Authors: Rozpędek-Kamińska Wioletta , Galita Grzegorz , Siwecka Natalia , Carroll Steven L. , Diehl John Alan , Kucharska Ewa , Pytel Dariusz , Majsterek Ireneusz
Published: April 2021

Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.
Indolyl Septanoside Synthesis for In Vivo Screening of Bacterial Septanoside Hydrolases
Authors: Pote Aditya R. , Pascual Sergi , Planas Antoni , Peczuh Mark W.
Published: April 2021

Building-up and breaking-down of carbohydrates are processes common to all forms of life. Glycoside hydrolases are a broad class of enzymes that play a central role in the cleavage of glycosidic bonds, which is fundamental to carbohydrate degradation. The large majority of substrates are five- and six-membered ring glycosides. Our interest in seven-membered ring septanose sugars has inspired the development of a way to search for septanoside hydrolase activity. Described here is a strategy for the discovery of septanoside hydrolases that uses synthetic indolyl septanosides as chromogenic substrates. Access to these tool compounds was enabled by a route where septanosyl halides act as glycosyl donors for the synthesis of the indolyl septanosides. The screening strategy leverages the known dimerization of 3-hydroxy-indoles to make colored dyes, as occurs when the β-galactosidase substrate X-Gal is hydrolyzed. Because screens in bacterial cells would enable searches in organisms that utilize heptoses or from metagenomics libraries, we also demonstrate that septanosides are capable of entering E. coli cells through the use of a BODIPY-labeled septanoside. The modularity of the indolyl septanoside synthesis should allow the screening of a variety of substrates that mimic natural structures via this general approach.
Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation
Authors: Suzuki Takahiro , Mori Aika , Maeno Takahiro , Arimatsu Rio , Ichimura Emi , Nishi Yuriko , Hisaeda Kouga , Yamaya Yuki , Kobayashi Ken , Nakamura Mako , Tatsumi Ryuichi , Ojima Koichi , Nishimura Takanori
Published: April 2021

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear. Herein, we focused on netrin family members (netrin-1, -3, and -4) that compete with Sema3A in neurogenesis and osteogenesis. We examined whether netrins affect fast-twitch myotube generation by evaluating their expression in primary satellite cell cultures. Initially, netrins are upregulated during myogenic differentiation. Next, we compared the expression levels of netrins and their cell membrane receptors between soleus- and EDL-derived satellite cells; only netrin-1 showed higher expression in EDL-derived satellite cells than in soleus-derived satellite cells. We also performed netrin-1 knockdown experiments and additional experiments with recombinant netrin-1 in differentiated satellite cell-derived myoblasts. Netrin-1 knockdown in myoblasts substantially reduced fast-type myosin heavy chain (MyHC) expression; exogenous netrin-1 upregulated fast-type MyHC in satellite cells. Thus, netrin-1 synthesized in EDL-derived satellite cells may promote myofiber type commitment of fast muscles.
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction
Authors: Tropea Teresa , Nihlen Carina , Weitzberg Eddie , Lundberg Jon O. , Wareing Mark , Greenwood Susan L. , Sibley Colin P. , Cottrell Elizabeth C.
Published: April 2021

Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). The reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p < 0.001), and in both normal (p < 0.001) and FGR (p < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p < 0.0001) and FGR (p < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p < 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies.
HERV-Derived Ervpb1 Is Conserved in Simiiformes, Exhibiting Expression in Hematopoietic Cell Lineages Including Macrophages
Authors: Matsuzawa Ayumi , Lee Jiyoung , Nakagawa So , Itoh Johbu , Takahashi Ueda Mahoko , Mitsuhashi Satomi , Kochi Yuta , Kaneko-Ishino Tomoko , Ishino Fumitoshi
Published: April 2021

(1) Background: The ERVPb1 gene in humans is derived from an envelope (Env) gene of a human endogenous retrovirus group, HERV-P(b). The ERVPb1 gene reportedly has a conserved open reading frame (ORF) in Old World monkeys. Although its forced expression led to cell-fusion in an ex vivo cell culture system, like other Env-derived genes such as syncytin-1 and -2, its mRNA expression is not placenta-specific, but almost ubiquitous, albeit being quite low in human tissues and organs, implying a distinct role for ERVPb1. (2) Methods: To elucidate the cell lineage(s) in which the ERVPb1 protein is translated in human development, we developed a novel, highly sensitive system for detecting HERV-derived proteins/peptides expressed in the tissue differentiation process of human induced pluripotent stem cells (iPSCs). (3) Results: We first determined that ERVPb1 is also conserved in New World monkeys. Then, we showed that the ERVPb1 protein is translated from a uniquely spliced ERVPb1 transcript in hematopoietic cell lineages, including a subset of macrophages, and further showed that its mRNA expression is upregulated by lipopolysaccharide (LPS) stimulation in primary human monocytes. (4) Conclusions: ERVPb1 is unique to Simiiformes and actually translated in hematopoietic cell lineages, including a subset of macrophages.
Increased Osteocyte Lacunae Density in the Hypermineralized Bone Matrix of Children with Osteogenesis Imperfecta Type I
Authors: Mähr Matthias , Blouin Stéphane , Behanova Martina , Misof Barbara M. , Glorieux Francis H. , Zwerina Jochen , Rauch Frank , Hartmann Markus A. , Fratzl-Zelman Nadja
Published: April 2021

Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix and key orchestrators of bone metabolism. However, they are generally not characterized by conventional bone histomorphometry because of their location and the limited resolution of light microscopy. OI is characterized by disturbed bone homeostasis, matrix abnormalities and elevated bone matrix mineralization density. To gain further insights into osteocyte characteristics and bone metabolism in OI, we evaluated 2D osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging in transiliac bone biopsy samples from children with OI type I (n = 19) and age-matched controls (n = 24). The OLS characteristics were related to previously obtained, re-visited histomorphometric parameters. Moreover, we present pediatric bone mineralization density distribution reference data in OI type I (n = 19) and controls (n = 50) obtained with a field emission scanning electron microscope. Compared to controls, OI has highly increased OLS density in cortical and trabecular bone (+50.66%, +61.73%; both p < 0.001), whereas OLS area is slightly decreased in trabecular bone (−10.28%; p = 0.015). Correlation analyses show a low to moderate, positive association of OLS density with surface-based bone formation parameters and negative association with indices of osteoblast function. In conclusion, hyperosteocytosis of the hypermineralized OI bone matrix associates with abnormal bone cell metabolism and might further impact the mechanical competence of the bone tissue.
Complex Mechanisms of Antimony Genotoxicity in Budding Yeast Involves Replication and Topoisomerase I-Associated DNA Lesions, Telomere Dysfunction and Inhibition of DNA Repair
Authors: Litwin Ireneusz , Mucha Seweryn , Pilarczyk Ewa , Wysocki Robert , Maciaszczyk-Dziubinska Ewa
Published: April 2021

Antimony is a toxic metalloid with poorly understood mechanisms of toxicity and uncertain carcinogenic properties. By using a combination of genetic, biochemical and DNA damage assays, we investigated the genotoxic potential of trivalent antimony in the model organism Saccharomyces cerevisiae. We found that low doses of Sb(III) generate various forms of DNA damage including replication and topoisomerase I-dependent DNA lesions as well as oxidative stress and replication-independent DNA breaks accompanied by activation of DNA damage checkpoints and formation of recombination repair centers. At higher concentrations of Sb(III), moderately increased oxidative DNA damage is also observed. Consistently, base excision, DNA damage tolerance and homologous recombination repair pathways contribute to Sb(III) tolerance. In addition, we provided evidence suggesting that Sb(III) causes telomere dysfunction. Finally, we showed that Sb(III) negatively effects repair of double-strand DNA breaks and distorts actin and microtubule cytoskeleton. In sum, our results indicate that Sb(III) exhibits a significant genotoxic activity in budding yeast.