bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Cable Configuration on the Voltage Induced in Cable Screen during Work with One-Sidedly Ungrounded Cable Screen
Authors: Schött-Szymczak Aleksandra , Walczak Krzysztof
Published: July 2021

In the latest research, it has been proven that from the point of view of losses in a cable distribution line, the most advantageous operation is to work with two or one phase of metallic cable screen ungrounded. However, such an operation may cause changes in the network characteristics and thus the occurrence of undesirable phenomena. One of those characteristics is the overvoltages in those cable screens, which can lead to cable line damage. The simulation tests presented in this article are closely related to the unusual method of operation of the MV cable screens and their performance, and they address the question of whether in a given system ground fault overvoltages may be a significant threat to the operation of the cable. The research methods used to verify these risks are related to the simulation of the cable line operating states using the DIgSILENT PowerFactory program (DIgSILENT GmbH, Gomaringen, Germany). Overvoltage simulations were performed, taking into account changes in the network configuration, such as the method of cable screens grounding, the length of cable lines, the cross-section of the conductor and cable screen, or the method of operation of the neutral point. The results for the cable line modeled as a part of the MV network with the variables considered during the tests indicate the possible impact of the one-sidedly cable screen ungrounding on overvoltages in this cable screen. The obtained results at the level of a few kV in one-sidedly ungrounded cable screens show that the change of the configuration of the operation of these cable screens may affect the safety of the network operation.
Modeling the Dynamic Linkage between Renewable Energy Consumption, Globalization, and Environmental Degradation in South Korea: Does Technological Innovation Matter?
Authors: Adebayo Tomiwa Sunday , Coelho Manuel Francisco , Onbaşıoğlu Dilber Çağlar , Rjoub Husam , Mata Mário Nuno , Carvalho Paulo Viegas , Rita João Xavier , Adeshola Ibrahim
Published: July 2021

The present research assesses the influence of globalization and technological innovation on CO2 emissions in South Korea as well as taking into account the role of renewable energy consumption and energy consumption utilizing datasets between 1980 and 2018. The autoregressive distributed lag (ARDL) bounds testing method is utilized to assess long-run cointegration. The outcome of the ARDL bounds test confirmed cointegration among the series. Furthermore, the ARDL reveals that economic growth, energy consumption and globalization trigger environmental degradation while technological innovation improves the quality of the environment. In addition, the study employed the frequency domain causality test to capture causal linkage among the series. The major advantage of this approach is that causal linkage between series can be captured at the short, medium and long term, respectively. The outcomes of the causality test revealed that globalization, technological innovation, economic growth and energy use can predict CO2 emissions in South Korea.
Ultrathin Cu(In,Ga)Se2 Solar Cells with Ag/AlOx Passivating Back Reflector
Authors: de Wild Jessica , Birant Gizem , Brammertz Guy , Meuris Marc , Poortmans Jef , Vermang Bart
Published: July 2021

Ultrathin Cu(In,Ga)Se2 (CIGS) absorber layers of 550 nm were grown on Ag/AlOx stacks. The addition of the stack resulted in solar cells with improved fill factor, open circuit voltage and short circuit current density. The efficiency was increased from 7% to almost 12%. Photoluminescence (PL) and time resolved PL were improved, which was attributed to the passivating properties of AlOx. A current increase of almost 2 mA/cm2 was measured, due to increased light scattering and surface roughness. With time of flight—secondary ion mass spectroscopy, the elemental profiles were measured. It was found that the Ag is incorporated through the whole CIGS layer. Secondary electron microscopic images of the Mo back revealed residuals of the Ag/AlOx stack, which was confirmed by energy dispersive X-ray spectroscopy measurements. It is assumed to induce the increased surface roughness and scattering properties. At the front, large stains are visible for the cells with the Ag/AlOx back contact. An ammonia sulfide etching step was therefore applied on the bare absorber improving the efficiency further to 11.7%. It shows the potential of utilizing an Ag/AlOx stack at the back to improve both electrical and optical properties of ultrathin CIGS solar cells.
Photovoltaic Cleaning Optimization: A Simplified Theoretical Approach for Air to Water Generator (AWG) System Employment
Authors: Cattani Lucia , Cattani Paolo , Magrini Anna
Published: July 2021

Photovoltaic panel efficiency can be heavily affected by soiling, due to dust and other airborne particles, which can determine up to 50% of energy production loss. Generally, it is possible to reduce that impact by means of periodic cleaning, and one of the most efficient cleaning solutions is the use of demineralized water. As pauperization of traditional water sources is increasing, new technologies have been developed to obtain the needed water amount. Water extracted from the air using air to water generator (AWG) technology appears to be particularly suitable for panel cleaning, but its effective employment presents issues related to model selection, determining system size, and energy efficiency. To overcome such issues, the authors proposed a method to choose an AWG system for panel cleaning and to determine its size accordingly, based on a cleaning time optimization procedure and tailored to AWG peculiarities, with an aim to maximize energy production. In order to determine the energy loss due to soiling, a simplified semiempirical model (i.e., the DIrt method) was developed as well. The methodology, which also allows for energy saving due to an optimal cleaning frequency, was applied to a case study. The results show that the choice of the most suitable AWG model could prevent 83% of energy loss related to soling. These methods are the first example of a design tool for panel cleaning planning involving AWG technology.
Towards a Full Circular Economy in Biogas Plants: Sustainable Management of Digestate for Growing Biomass Feedstocks and Use as Biofertilizer
Authors: Jurgutis Linas , Šlepetienė Alvyra , Šlepetys Jonas , Cesevičienė Jurgita
Published: July 2021

The digestate is a prospective biofertilizer and potential source of income for many biogas plants worldwide. However, its actual impact on the soil properties and biomass yield is still unexploited. The different digestates from eight agricultural biogas plants were researched in terms of their chemical composition and the fertilizing potential. The results obtained from digestate chemical analysis indicate that the digestate biomass had large amount of nitrogen (up to 73 g kg−1 fresh mass) and potassium (up to 25 g kg−1 fresh mass). The value of the digestate was estimated in the range of 2.88–7.89 EUR Mg−1 for liquid digestate and 7.62–13.61 EUR Mg−1 for solid digestate based on the commercial fertilizer market price of nitrogen, potassium phosphorus, organic carbon, Cu, Zn, Fe and Mg. The digestate produced at the 1 MW biogas plant is worth EUR 941–2095 per day in addition to energy sales income. The application of digestate on low-fertility land in areas close to the biogas plant allows the production of up to three-fold more biomass suitable for biogas production. The digestate’s application on semi-natural grass biomass production in the low-fertility soils near the biogas plants could be an alternative strategy for the biogas plant feedstock portfolio diversification.
Pore-Scale Investigation on Natural Convection Melting in a Square Cavity with Gradient Porous Media
Authors: Huang Jiangxu , He Kun , Wang Lei
Published: July 2021

In this paper, natural convection melting in a square cavity with gradient porous media is numerically studied at pore-scale level by adopting the lattice Boltzmann method. To generate the gradient porous media, a Monte Carlo technique based on the random sampling principle is used. The effects of several factors, such as Rayleigh number, gradient porosity structure, gradient direction, and particle diameters on natural convection melting are investigated in detail. Based on the numerical data, it is observed that the thermal performance of the gradient porous media always depends on the Rayleigh number and, specifically, as the Rayleigh number is set to 106, the total melting time obtained for the case of the negative gradient porous media is always shorter than the cases of positive gradient and uniform porous media. However, if the Rayleigh number is equal to 104, at which the heat transfer is dominated by the heat conduction, it is noted that the performance of the positive gradient porous media is better than the other cases. To have a better understand on this point, various simulations are also performed and we found that there usually exists a critical value of Rayleigh number to determine the thermal performance of the gradient porous media. Moreover, our numerical results also show that the influence of the particle diameter on the liquid fraction is insignificant as Rayleigh number is set to 104, while it has a great impact on the liquid fraction when Rayleigh number equals 106.
The Potential of the Reed as a Regenerative Building Material—Characterisation of Its Durability, Physical, and Thermal Performances
Authors: Malheiro Raphaele , Ansolin Adriana , Guarnier Christiane , Fernandes Jorge , Amorim Maria Teresa , Silva Sandra Monteiro , Mateus Ricardo
Published: July 2021

Knowing the properties of vernacular materials is crucial to heritage conservation and to develop innovative solutions. Reed, considered to be a carbon-neutral and a carbon dioxide sink material, has been used for centuries for diverse uses. Its high availability and properties made it a popular building material, including in Portuguese vernacular architecture. An experimental investigation was conducted to evaluate the physical performance, thermal performance, and durability of the reed found in Portugal since the characterisation of this material was not found in previous studies. The influence of geometric characteristics and the presence of nodes on these properties were also analysed, and the results showed that they are irrelevant. The studied reeds were found to have an adequate thermal performance to be used as thermal insulation. Their thermal resistance (1.8 m2·°C/W) and thermal conductivity (0.06 W/m·°C) are under the requirements defined by Portuguese regulations on thermal insulation materials. Overall, the physical characteristics (moisture content, density, and retraction) are compatible to its use in the construction. Concerning durability, there was only a trend for mould growth in particular environments. The results provide valuable data to be considered in the development of new construction products based on this natural and renewable material. Additionally, considering the studied samples, the reed found in Portugal has characteristics suitable for use as a building material, especially as a thermal insulation material.
A Consensus Algorithm for Multi-Objective Battery Balancing
Authors: Barreras Jorge Varela , de Castro Ricardo , Wan Yihao , Dragicevic Tomislav
Published: July 2021

Batteries stacks are made of cells in certain series-parallel arrangements. Unfortunately, cell performance degrades over time in terms of capacity, internal resistance, or self-discharge rate. In addition, degradation rates are heterogeneous, leading to cell-to-cell variations. Balancing systems can be used to equalize those differences. Dissipative or non-dissipative systems, so-called passive or active balancing, can be used to equalize either voltage at end-of-charge, or state-of-charge (SOC) at all times. While passive balancing is broadly adopted by industry, active balancing has been mostly studied in academia. Beyond that, an emerging research field is multi-functional balancing, i.e., active balancing systems that pursue additional goals on top of SOC equalization, such as equalization of temperature, power capability, degradation rates, or losses minimization. Regardless of their functionality, balancing circuits are based either on centralized or decentralized control systems. Centralized control entails difficult expandability and single point of failure issues, while decentralized control has severe controllability limitations. As a shift in this paradigm, here we present for the first time a distributed multi-objective control algorithm, based on a multi-agent consensus algorithm. We implement and validate the control in simulations, considering an electro-thermal lithium-ion battery model and an electric vehicle model parameterized with experimental data. Our results show that our novel multi-functional balancing can enhance the performance of batteries with substantial cell-to-cell differences under the most demanding operating conditions, i.e., aggressive driving and DC fast charging (2C). Driving times are extended (>10%), charging times are reduced (>20%), maximum cell temperatures are decreased (>10 °C), temperature differences are lowered (~3 °C rms), and the occurrence of low voltage violations during driving is reduced (>5×), minimizing the need for power derating and enhancing the user experience. The algorithm is effective, scalable, flexible, and requires low implementation and tuning effort, resulting in an ideal candidate for industry adoption.
Centralized Control of Distribution Networks with High Penetration of Renewable Energies
Authors: Zarco-Soto Fco. Javier , Zarco-Periñán Pedro J. , Martínez-Ramos Jose L.
Published: July 2021

Distribution networks were conceived to distribute the energy received from transmission and subtransmission to supply passive loads. This approach, however, is not valid anymore due to the presence of distributed generation, which is mainly based on renewable energies, and the increased number of plug-in electric vehicles that are connected at this voltage level for domestic use. In this paper the ongoing transition that distribution networks face is addressed. Whereas distributed renewable energy sources increase nodal voltages, electric vehicles result in demand surges higher than the load predictions considered when planning these networks, leading to congestion in distribution lines and transformers. Additionally, centralized control techniques are analyzed to reduce the impact of distributed generation and electric vehicles and increase their effective integration. A classification of the different methodologies applied to the problems of voltage control and congestion management is presented.
Self-Sufficiency and Energy Savings of Renewable Thermal Energy Systems for an Energy-Sharing Community
Authors: Kim Min-Hwi , An Youngsub , Joo Hong-Jin , Lee Dong-Won , Yun Jae-Ho
Published: July 2021

Due to increased grid problems caused by renewable energy systems being used to realize zero energy buildings and communities, the importance of energy sharing and self-sufficiency of renewable energy also increased. In this study, the energy performance of an energy-sharing community was investigated to improve its energy efficiency and renewable energy self-sufficiency. For a case study, a smart village was selected via detailed simulation. In this study, the thermal energy for cooling, heating, and domestic hot water was produced by ground source heat pumps, which were integrated with thermal energy storage (TES) with solar energy systems. We observed that the ST system integrated with TES showed higher self-sufficiency with grid interaction than the PV and PVT systems. This was due to the heat pump system being connected to thermal energy storage, which was operated as an energy storage system. Consequently, we also found that the ST system had a lower operating energy, CO2 emissions, and operating costs compared with the PV and PVT systems.
Development and Testing of a 252 kV/2500 A-40 kA Multi-Break Bus-Coupler Fast Vacuum Circuit Breaker
Authors: Ma Kui , Yao Xiaofei , Zhang Luyang , Ai Shaogui , Wang Shuhong , Wang Jianhua , Geng Yingsan , Liu Zhiyuan
Published: July 2021

It is effective to open the bus-coupler circuit breaker in case of a short-circuit fault. A fast vacuum circuit breaker (FVCB) is an ideal bus-coupler circuit breaker due to its high velocity. The objective of this study was to develop and test a 252 kV/2500 A-40 kA multi-break bus-coupler FVCB. The 252 kV FVCB contained 12 FVCB units. Each phase consisted of four FVCB units connected in series. Each FVCB unit had an electromagnetic repulsion mechanism with an average opening velocity reaching 6.5 m/s. Test results showed the opening time was 1.11 ± 0.08 ms. The capacitance of the voltage grading capacitor of each break was determined to be 10 nF. The prototype 252 kV bus-coupler FVCB passed all partial test duties according to the IEC 62271-100: 2008 and IEC 62271-1: 2007 standards, which include an insulation test and a terminal fault test among others. A 252 kV/2500 A-40 kA multi-break bus-coupler FVCB can be used to quickly cut off a short-circuit fault and effectively limit a short-circuit current.
Induced Volatile Emissions, Photosynthetic Characteristics, and Pigment Content in Juglans regia Leaves Infected with the Erineum-Forming Mite Aceria erinea
Authors: Popitanu Corina , Lupitu Andreea , Copolovici Lucian , Bungău Simona , Niinemets Ülo , Copolovici Dana Maria
Published: July 2021

Persian walnut (Juglans regia L., Juglandaceae), one of the essential nut crops, is affected by different diseases, including mite attacks which result in gall and erineum formation. As the proportion of leaf area covered by mite galls or erineum is typically relatively low, the impact on tree photosynthetic productivity is often considered minor, and no pest control management is usually suggested. However, the effect of erineum-forming mites on walnut photosynthesis might be disproportionately larger than can be predicted from the leaf area impacted. In the present study, we studied how the foliage photosynthetic characteristics, pigment contents, and stress-induced volatile organic compounds scaled with the severity of infection varied from 0% (control trees) to 9.9%, by erineum-forming mite Aceria erinea in J. regia. Both leaf net assimilation rate (up to 75% reduction) and stomatal conductance (up to 82%) decreased disproportionately, increasing infection severity. Leaf total chlorophyll and β-carotene contents also decreased with infection severity, although the reduction was less than for photosynthetic characteristics (28% for chlorophyll and 25% for β-carotene). The infection induced significant emissions of green leaves volatiles ((Z)-3-hexenol, (E)-2-hexenal, (Z)-3-hexenyl acetate and 1-hexanol), monoterpenes and the homoterpene 3-(E)-4,8-dimethyl-1,3,7-nonatriene, and these emissions scaled positively with the percentage of leaf area infected. These results collectively indicate that erineum-forming mite infection of walnut leaves results in profound modifications in foliage physiological characteristics that can significantly impact tree photosynthetic productivity.
Photogrammetric Prediction of Rock Fracture Properties and Validation with Metric Shear Tests
Authors: Uotinen Lauri , Torkan Masoud , Baghbanan Alireza , Hernández Enrique Caballero , Rinne Mikael
Published: July 2021

An accurate understanding of jointed rock mass behavior is important in many applications ranging from deep geological disposal of nuclear waste, to deep mining, and to urban geoengineering projects. The roughness of rock fractures and the matching of the fracture surfaces are the key contributors to the shear strength of rock fractures. In this research, push shear tests with three normal stress levels of 3.6, 6.0, and 8.5 kPa were conducted on two granite samples with artificially induced well-matching tensile fractures with sizes of 500 mm × 250 mm and 1000 mm × 500 mm. The large sample reached on average a −60% weaker peak shear stress than the medium-sized sample, and a strong negative scale effect was observed in the peak shear strength. The roughness of the surfaces was measured using a profilometer and photogrammetry. The scale-corrected profilometer-based method (joint roughness coefficient, JRC) underestimates the peak friction angle for the medium-sized slabs by −27% for the medium sample and −9% for the large sample. The photogrammetry-based (Z′2) method produces an estimate with −7% (medium) and + 12% (large) errors. The photogrammetry-based Z′2 is an objective method that consistently produces usable estimates for the JRC and peak friction angle.
QTL Mapping and Diurnal Transcriptome Analysis Identify Candidate Genes Regulating Brassica napus Flowering Time
Authors: Song Jurong , Li Bao , Cui Yanke , Zhuo Chenjian , Gu Yuanguo , Hu Kaining , Wen Jing , Yi Bin , Shen Jinxiong , Ma Chaozhi , Fu Tingdong , Tu Jinxing
Published: July 2021

Timely flowering is important for seed formation and maximization of rapeseed (Brassica napus) yield. Here, we performed flowering-time quantitative trait loci (QTL) mapping using a double haploid (DH) population grown in three environments to study the genetic architecture. Brassica 60 K Illumina Infinium™ single nucleotide polymorphism (SNP) array and simple sequence repeat (SSR) markers were used for genotyping of the DH population, and a high-density genetic linkage map was constructed. QTL analysis of flowering time from the three environments revealed five consensus QTLs, including two major QTLs. A major QTL located on chromosome A03 was detected specifically in the semi-winter rapeseed growing region, and the one on chromosome C08 was detected in all environments. Ribonucleic acid sequencing (RNA-seq) was performed on the parents’ leaves at seven time-points in a day to determine differentially expressed genes (DEGs). The biological processes and pathways with significant enrichment of DEGs were obtained. The DEGs in the QTL intervals were analyzed, and four flowering time-related candidate genes were found. These results lay a foundation for the genetic regulation of rapeseed flowering time and create a rapeseed gene expression library for seven time-points in a day.
A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters
Authors: Mingyar Erik , Mühling Lucas , Kulik Andreas , Winkler Anika , Wibberg Daniel , Kalinowski Jörn , Blin Kai , Weber Tilmann , Wohlleben Wolfgang , Stegmann Evi
Published: July 2021

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10.
TGF-β Signaling: From Tissue Fibrosis to Tumor Microenvironment
Authors: Chung Jeff Yat-Fai , Chan Max Kam-Kwan , Li Jane Siu-Fan , Chan Alex Siu-Wing , Tang Philip Chiu-Tsun , Leung Kam-Tong , To Ka-Fai , Lan Hui-Yao , Tang Patrick Ming-Kuen
Published: July 2021

Transforming growth factor-β (TGF-β) signaling triggers diverse biological actions in inflammatory diseases. In tissue fibrosis, it acts as a key pathogenic regulator for promoting immunoregulation via controlling the activation, proliferation, and apoptosis of immunocytes. In cancer, it plays a critical role in tumor microenvironment (TME) for accelerating invasion, metastasis, angiogenesis, and immunosuppression. Increasing evidence suggest a pleiotropic nature of TGF-β signaling as a critical pathway for generating fibrotic TME, which contains numerous cancer-associated fibroblasts (CAFs), extracellular matrix proteins, and remodeling enzymes. Its pathogenic roles and working mechanisms in tumorigenesis are still largely unclear. Importantly, recent studies successfully demonstrated the clinical implications of fibrotic TME in cancer. This review systematically summarized the latest updates and discoveries of TGF-β signaling in the fibrotic TME.
Expression of RUNX1-JAK2 in Human Induced Pluripotent Stem Cell-Derived Hematopoietic Cells Activates the JAK-STAT and MYC Pathways
Authors: Fortschegger Klaus , Husa Anna-Maria , Schinnerl Dagmar , Nebral Karin , Strehl Sabine
Published: July 2021

A heterogeneous genetic subtype of B-cell precursor acute lymphoblastic leukemia is driven by constitutive kinase-activation, including patients with JAK2 fusions. In our study, we model the impact of a novel JAK2 fusion protein on hematopoietic development in human induced pluripotent stem cells (hiPSCs). We insert the RUNX1-JAK2 fusion into one endogenous RUNX1 allele through employing in trans paired nicking genome editing. Tagging of the fusion with a degron facilitates protein depletion using the heterobifunctional compound dTAG-13. Throughout in vitro hematopoietic differentiation, the expression of RUNX1-JAK2 is driven by endogenous RUNX1 regulatory elements at physiological levels. Functional analysis reveals that RUNX1-JAK2 knock-in cell lines yield fewer hematopoietic progenitors, due to RUNX1 haploinsufficiency. Nevertheless, these progenitors further differentiate toward myeloid lineages to a similar extent as wild-type cells. The expression of the RUNX1-JAK2 fusion protein only elicits subtle effects on myeloid differentiation, and is unable to transform early hematopoietic progenitors. However, phosphoprotein and transcriptome analyses reveal that RUNX1-JAK2 constitutively activates JAK-STAT signaling in differentiating hiPSCs and at the same time upregulates MYC targets—confirming the interaction between these pathways. This proof-of-principle study indicates that conditional expression of oncogenic fusion proteins in combination with hematopoietic differentiation of hiPSCs may be applicable to leukemia-relevant disease modeling.
Haplotype Analysis of BADH1 by Next-Generation Sequencing Reveals Association with Salt Tolerance in Rice during Domestication
Authors: Min Myeong-Hyeon , Maung Thant Zin , Cao Yuan , Phitaktansakul Rungnapa , Lee Gang-Seob , Chu Sang-Ho , Kim Kyu-Won , Park Yong-Jin
Published: July 2021

Betaine aldehyde dehydrogenase 1 (BADH1), a paralog of the fragrance gene BADH2, is known to be associated with salt stress through the accumulation of synthesized glycine betaine (GB), which is involved in the response to abiotic stresses. Despite the unclear association between BADH1 and salt stress, we observed the responses of eight phenotypic characteristics (germination percentage (GP), germination energy (GE), germination index (GI), mean germination time (MGT), germination rate (GR), shoot length (SL), root length (RL), and total dry weight (TDW)) to salt stress during the germination stage of 475 rice accessions to investigate their association with BADH1 haplotypes. We found a total of 116 SNPs and 77 InDels in the whole BADH1 gene region, representing 39 haplotypes. Twenty-nine haplotypes representing 27 mutated alleles (two InDels and 25 SNPs) were highly (p < 0.05) associated with salt stress, including the five SNPs that have been previously reported to be associated with salt tolerance. We observed three predominant haplotypes associated with salt tolerance, Hap_2, Hap_18, and Hap_23, which were Indica specific, indicating a comparatively high number of rice accessions among the associated haplotypes. Eight plant parameters (phenotypes) also showed clear responses to salt stress, and except for MGT (mean germination time), all were positively correlated with each other. Different signatures of domestication for BADH1 were detected in cultivated rice by identifying the highest and lowest Tajima’s D values of two major cultivated ecotypes (Temperate Japonica and Indica). Our findings on these significant associations and BADH1 evolution to plant traits can be useful for future research development related to its gene expression.
Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects
Authors: Mansur Fernanda , Teles e Silva André Luiz , Gomes Ana Karolyne Santos , Magdalon Juliana , de Souza Janaina Sena , Griesi-Oliveira Karina , Passos-Bueno Maria Rita , Sertié Andréa Laurato
Published: July 2021

In recent years, accumulating evidence has shown that the innate immune complement system is involved in several aspects of normal brain development and in neurodevelopmental disorders, including autism spectrum disorder (ASD). Although abnormal expression of complement components was observed in post-mortem brain samples from individuals with ASD, little is known about the expression patterns of complement molecules in distinct cell types in the developing autistic brain. In the present study, we characterized the mRNA and protein expression profiles of a wide range of complement system components, receptors and regulators in induced pluripotent stem cell (iPSC)-derived neural progenitor cells, neurons and astrocytes of individuals with ASD and neurotypical controls, which constitute in vitro cellular models that recapitulate certain features of both human brain development and ASD pathophysiology. We observed that all the analyzed cell lines constitutively express several key complement molecules. Interestingly, using different quantification strategies, we found that complement C4 mRNA and protein are expressed in significantly lower levels by astrocytes derived from ASD individuals compared to control astrocytes. As astrocytes participate in synapse elimination, and diminished C4 levels have been linked to defective synaptic pruning, our findings may contribute to an increased understanding of the atypically enhanced brain connectivity in ASD.
Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation
Authors: Gramlich Oliver W. , Godwin Cheyanne R. , Wadkins David , Elwood Benjamin W. , Kuehn Markus H.
Published: July 2021

Glaucoma is a leading cause of irreversible blindness worldwide, and increased intraocular pressure (IOP) is a major risk factor. We aimed to determine if early functional and molecular differences in the glaucomatous retina manifest before significant retinal ganglion cell (RGC) loss is apparent. Adenoviral vectors expressing a pathogenic form of myocilin (Ad5.MYOC) were used to induce IOP elevation in C57BL/6 mice. IOP and pattern electroretinograms (pERG) were recorded, and retinas were prepared for RNA sequencing, immunohistochemistry, or to determine RGC loss. Ocular injection of Ad5.MYOC leads to reliable IOP elevation, resulting in significant loss of RGC after nine weeks. A significant decrease in the pERG amplitude was evident in eyes three weeks after IOP elevation. Retinal gene expression analysis revealed increased expression for 291 genes related to complement cascade, inflammation, and antigen presentation in hypertensive eyes. Decreased expression was found for 378 genes associated with the γ-aminobutyric acid (GABA)ergic and glutamatergic systems and axon guidance. These data suggest that early functional changes in RGC might be due to reduced GABAA receptor signaling and neuroinflammation that precedes RGC loss in this glaucoma model. These initial changes may offer new targets for early detection of glaucoma and the development of new interventions.
Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient
Authors: Bresadola Luisa , Weber David , Ritzel Christoph , Löwer Martin , Bukur Valesca , Akilli-Öztürk Özlem , Becker Julia , Mehanna Hisham , Schrörs Barbara , Vascotto Fulvia , Sahin Ugur , Kong Anthony
Published: July 2021

Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.
Adenosine Receptor Reserve and Long-Term Potentiation: Unconventional Adaptive Mechanisms in Cardiovascular Diseases?
Authors: Guieu Régis , Brignole Michele , Deharo Jean Claude , Deharo Pierre , Mottola Giovanna , Groppelli Antonella , Paganelli Franck , Ruf Jean
Published: July 2021

While the concept of a receptor reserve (spare receptors) is old, their presence on human cells as an adaptive mechanism in cardiovascular disease is a new suggestion. The presence of spare receptors is suspected when the activation of a weak fraction of receptors leads to maximal biological effects, in other words, when the half-maximal effective concentration (EC50) for a biological effect (cAMP production, for example) is lower than the affinity (KD) of the ligand for a receptor. Adenosine is an ATP derivative that strongly impacts the cardiovascular system via its four membrane receptors, named A1R, A2AR, A2BR, and A3R, with the A1R being more particularly involved in heart rhythm, while the A2AR controls vasodilation. After a general description of the tools necessary to explore the presence of spare receptors, this review focuses on the consequences of the presence of spare adenosine receptors in cardiovascular physiopathology. Finally, the role of the adenosinergic system in the long-term potentiation and its possible consequences on the physiopathology are also mentioned.
Photobiomodulation by Near-Infrared 980-nm Wavelengths Regulates Pre-Osteoblast Proliferation and Viability through the PI3K/Akt/Bcl-2 Pathway
Authors: Agas Dimitrios , Hanna Reem , Benedicenti Stefano , De Angelis Nicola , Sabbieti Maria Giovanna , Amaroli Andrea
Published: July 2021

Background: bone tissue regeneration remains a current challenge. A growing body of evidence shows that mitochondrial dysfunction impairs osteogenesis and that this organelle may be the target for new therapeutic options. Current literature illustrates that red and near-infrared light can affect the key cellular pathways of all life forms through interactions with photoacceptors within the cells’ mitochondria. The current study aims to provide an understanding of the mechanisms by which photobiomodulation (PBM) by 900-nm wavelengths can induce in vitro molecular changes in pre-osteoblasts. Methods: The PubMed, Scopus, Cochrane, and Scholar databases were used. The manuscripts included in the narrative review were selected according to inclusion and exclusion criteria. The new experimental set-up was based on irradiation with a 980-nm laser and a hand-piece with a standard Gaussian and flat-top beam profile. MC3T3-E1 pre-osteoblasts were irradiated at 0.75, 0.45, and 0.20 W in continuous-wave emission mode for 60 s (spot-size 1 cm2) and allowed to generate a power density of 0.75, 0.45, and 0.20 W/cm2 and a fluence of 45, 27, and 12 J/cm2, respectively. The frequency of irradiation was once, three times (alternate days), or five times (every day) per week for two consecutive weeks. Differentiation, proliferation, and cell viability and their markers were investigated by immunoblotting, immunolabelling, fluorescein-FragELTM-DNA, Hoechst staining, and metabolic activity assays. Results and conclusions: The 980-nm wavelength can photobiomodulate the pre-osteoblasts, regulating their metabolic schedule. The cellular signal activated by 45 J/cm2, 0.75 W and 0.75 W/cm2 consist of the PI3K/Akt/Bcl-2 pathway; differentiation markers were not affected, nor do other parameters seem to stimulate the cells. Our previous and present data consistently support the window effect of 980 nm, which has also been described in extracted mitochondria, through activation of signalling PI3K/Akt/Bcl-2 and cyclin family, while the Wnt and Smads 2/3-β-catenin pathway was induced by 55 J/cm2, 0.9 W and 0.9 W/cm2.
Kaiso Regulates DNA Methylation Homeostasis
Authors: Kaplun Darya , Starshin Alexey , Sharko Fedor , Gainova Kristina , Filonova Galina , Zhigalova Nadezhda , Mazur Alexander , Prokhortchouk Egor , Zhenilo Svetlana
Published: July 2021

Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT repressive complexes affecting histone modifications. On the other hand, the deficiency of Kaiso resulted in reduced methylation of ICR in H19/Igf2 locus and Oct4 promoter in mouse embryonic fibroblasts. However, nothing is known about how Kaiso influences DNA methylation at the genome level. Here we show that deficiency of Kaiso led to whole-genome hypermethylation, using Kaiso deficient human renal cancer cell line obtained via CRISPR/CAS9 genome editing. However, Kaiso serves to protect genic regions, enhancers, and regions with a low level of histone modifications from demethylation. We detected hypomethylation of binding sites for Oct4 and Nanog in Kaiso deficient cells. Kaiso immunoprecipitated with de novo DNA methyltransferases DNMT3a/3b, but not with maintenance methyltransferase DNMT1. Thus, Kaiso may attract methyltransferases to surrounding regions and modulate genome methylation in renal cancer cells apart from being methyl DNA binding protein.
Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch
Authors: Zhang Qiaojuan , Henry Gwendolyn , Chen Yong
Published: July 2021

Itch is a clinical problem that leaves many sufferers insufficiently treated, with over 20 million cases in the United States. This is due to incomplete understanding of its molecular, cellular, and cell-to-cell signaling mechanisms. Transient receptor potential (TRP) ion channels are involved in several sensory modalities including pain, vision, taste, olfaction, hearing, touch, and thermosensation, as well as itch. Relative to the extensive studies on TRPV1 and TRPA1 ion channels in itch modulation, TRPV4 has received relatively little research attention and its mechanisms have remained poorly understood until recently. TRPV4 is expressed in ganglion sensory neurons and a variety of skin cells. Growing evidence in the past few years strongly suggests that TRPV4 in these cells contributes to acute and chronic disease-associated itch. This review focuses on the current experimental evidence involving TRPV4 in itch under pathophysiological conditions and discusses its possible cellular and molecular mechanisms.
Action of Multiple Rice β-Glucosidases on Abscisic Acid Glucose Ester
Authors: Kongdin Manatchanok , Mahong Bancha , Lee Sang-Kyu , Shim Su-Hyeon , Jeon Jong-Seong , Ketudat Cairns James R.
Published: July 2021

Conjugation of phytohormones with glucose is a means of modulating their activities, which can be rapidly reversed by the action of β-glucosidases. Evaluation of previously characterized recombinant rice β-glucosidases found that nearly all could hydrolyze abscisic acid glucose ester (ABA-GE). Os4BGlu12 and Os4BGlu13, which are known to act on other phytohormones, had the highest activity. We expressed Os4BGlu12, Os4BGlu13 and other members of a highly similar rice chromosome 4 gene cluster (Os4BGlu9, Os4BGlu10 and Os4BGlu11) in transgenic Arabidopsis. Extracts of transgenic lines expressing each of the five genes had higher β-glucosidase activities on ABA-GE and gibberellin A4 glucose ester (GA4-GE). The β-glucosidase expression lines exhibited longer root and shoot lengths than control plants in response to salt and drought stress. Fusions of each of these proteins with green fluorescent protein localized near the plasma membrane and in the apoplast in tobacco leaf epithelial cells. The action of these extracellular β-glucosidases on multiple phytohormones suggests they may modulate the interactions between these phytohormones.
The MEK5/ERK5 Pathway in Health and Disease
Authors: Paudel Rupesh , Fusi Lorenza , Schmidt Marc
Published: July 2021

The MEK5/ERK5 mitogen-activated protein kinases (MAPK) cascade is a unique signaling module activated by both mitogens and stress stimuli, including cytokines, fluid shear stress, high osmolarity, and oxidative stress. Physiologically, it is mainly known as a mechanoreceptive pathway in the endothelium, where it transduces the various vasoprotective effects of laminar blood flow. However, it also maintains integrity in other tissues exposed to mechanical stress, including bone, cartilage, and muscle, where it exerts a key function as a survival and differentiation pathway. Beyond its diverse physiological roles, the MEK5/ERK5 pathway has also been implicated in various diseases, including cancer, where it has recently emerged as a major escape route, sustaining tumor cell survival and proliferation under drug stress. In addition, MEK5/ERK5 dysfunction may foster cardiovascular diseases such as atherosclerosis. Here, we highlight the importance of the MEK5/ERK5 pathway in health and disease, focusing on its role as a protective cascade in mechanical stress-exposed healthy tissues and its function as a therapy resistance pathway in cancers. We discuss the perspective of targeting this cascade for cancer treatment and weigh its chances and potential risks when considering its emerging role as a protective stress response pathway.
Proinflammatory and Hepatic Features Related to Morbidity and Fatal Outcomes in COVID-19 Patients
Authors: Ramos-Lopez Omar , San-Cristobal Rodrigo , Martinez-Urbistondo Diego , Micó Víctor , Colmenarejo Gonzalo , Villares-Fernandez Paula , Daimiel Lidia , Martinez J. Alfredo
Published: July 2021

Objective: to screen putative associations between liver markers and proinflammatory-related features concerning infectious morbidity and fatal outcomes in COVID-19 patients. Methods: a total of 2094 COVID-19 positive patients from the COVID-DATA-SAFE-LIFES cohort (HM hospitals consortium) were classified according to median values of hepatic, inflammatory, and clinical indicators. Logistic regression models were fitted and ROC cures were generated to explain disease severity and mortality. Results: intensive care unit (ICU) assistance plus death outcomes were associated with liver dysfunction, hyperinflammation, respiratory insufficiency, and higher associated comorbidities. Four models including age, sex, neutrophils, D-dimer, oxygen saturation lower than 92%, C-reactive protein (CRP), Charlson Comorbidity Index (CCI), FIB-4 and interactions with CRP, neutrophils, and CCI explained ICU plus death variance in more than 28%. The predictive values of ROC curves were: FIB-4 (0.7339), AST/ALT ratio (0.7107), CRP (0.7003), CCI index (0.6778), neutrophils (0.6772), and platelets (0.5618) concerning ICU plus death outcomes. Conclusions: the results of this research revealed that liver and proinflammatory features are important determinants of COVID-19 morbidity and fatal outcomes, which could improve the current understanding of the COVID-19 physiopathology as well as to facilitate the clinical management and therapy decision-making of this disease under a personalized medicine scope.
Exercise and the Risk of Dementia in Patients with Newly Diagnosed Atrial Fibrillation: A Nationwide Population-Based Study
Authors: Lim Jaehyun , Lee So-Ryoung , Choi Eue-Keun , Han Kyung-Do , Jung Jin-Hyung , Ahn Hyo-Jeong , Yun Jun Pil , Kwon Soonil , Oh Seil , Lip Gregory Y. H.
Published: July 2021

Background: It is unclear whether exercise would reduce dementia in patients with a new diagnosis of atrial fibrillation (AF). Therefore, we aimed to evaluate the association between the change in physical activity (PA) before and after new-onset AF and the risk of incident dementia. Methods: Using the Korean National Health Insurance Service database, we enrolled a total of 126,555 patients with newly diagnosed AF between 2010 and 2016, who underwent health examinations within two years before and after their diagnosis of AF. The patients were divided into four groups: persistent non-exercisers, exercise starters, exercise quitters, and exercise maintainers. Results: Based on a total of 396,503 person-years of follow-up, 5943 patients were diagnosed with dementia. Compared to persistent non-exercisers, exercise starters (adjusted hazard ratio (aHR) 0.87; 95% confidence interval (CI) 0.81–0.94), and exercise maintainers (aHR 0.66; 95% CI 0.61–0.72) showed a lower risk of incident dementia; however, the risk was similar in exercise quitters (aHR 0.98; 95% CI 0.92–1.05) (p-trend < 0.001). There was a J-shaped relationship between the dose of exercise and the risk of dementia, with the risk reduction maximized at 5–6 times per week of moderate-to-vigorous PA among exercise starters. Conclusion: Patients who initiated or continued regular exercise after diagnosis of AF were associated with a lower risk of dementia than persistent non-exercisers, with no risk reduction associated with exercise cessation. Our findings may provide evidence for the benefit of exercise prescription to patients with new-onset AF to prevent incident dementia regardless of their current exercise status.
Colorectal Cancer Risk in Women with Gynecologic Cancers—A Population Retrospective Cohort Study
Authors: Liao Szu-Chia , Yeh Hong-Zen , Chang Chi-Sen , Chen Wei-Chih , Muo Chih-Hsin , Sung Fung-Chang
Published: July 2021

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.