bluuebunny/crossref_metadata_2025 huggingface dataset:
A 3D Cell Death Assay to Quantitatively Determine Ferroptosis in Spheroids
Authors: Demuynck Robin , Efimova Iuliia , Lin Abraham , Declercq Heidi , Krysko Dmitri V.
Published: March 2020

The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is largely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug screening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged to be a better model of the in vivo environment, but detailed cell death assays for 3D cultures (including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis method, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types including ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses Sytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in spheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton X-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from all cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that 2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death induction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death type in 3D cultures, including spheroids.
Carbonic Anhydrase III Promotes Cell Migration and Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinoma
Authors: Chu Yin-Hung , Su Chun-Wen , Hsieh Yih-Shou , Chen Pei-Ni , Lin Chiao-Wen , Yang Shun-Fa
Published: March 2020

Epithelial–mesenchymal transition (EMT) is strongly correlated with tumor metastasis and contains several protein markers, such as E-cadherin. Carbonic anhydrase III (CA III) exhibits low carbon dioxide hydratase activity in cancer. However, the detailed mechanisms of CA III and their roles in oral cancer are still unknown. This study established a CA III-overexpressed stable clone and observed the expression of CA III protein in human SCC-9 and SAS oral cancer cell lines. The migration and invasion abilities were determined using a Boyden chamber assay. Our results showed that the overexpression of CA III protein significantly increased the migration and invasion abilities in oral cancer cells. Moreover, a whole genome array analysis revealed that CA III regulated epithelial–mesenchymal transition by reducing the expression of epithelial markers. Data from the GEO database also demonstrated that CA III mRNA is negatively correlated with CDH1 mRNA. Mechanistically, CA III increased the cell motility of oral cancer cells through the FAK/Src signaling pathway. In conclusion, this suggests that CA III promotes EMT and cell migration and is potentially related to the FAK/Src signaling pathway in oral cancer.
Clinical Significance of Tumor Size, Pathological Invasion Sites Including Urinary Collecting System and Clinically Detected Renal Vein Thrombus as Predictors for Recurrence in pT3a Localized Renal Cell Carcinoma
Authors: Shimizu Takuto , Miyake Makito , Hori Shunta , Iida Kota , Ichikawa Kazuki , Sakamoto Keiichi , Miyamoto Tatsuki , Nakai Yasushi , Inoue Takeshi , Anai Satoshi , Tanaka Nobumichi , Fujimoto Kiyohide
Published: March 2020

The recent eighth tumor-node-metastasis (TMN) staging system classifies renal cell carcinoma (RCC) with perirenal fat invasion (PFI), renal sinus fat invasion (SFI), or renal vein invasion (RVI) as stage pT3a. However, limited data are available on whether these sites have similar prognostic value or recurrence rate. We investigated the recurrence rate based on tumor size, pathological invasion sites including urinary collecting system invasion (UCSI), and clinically detected renal vein thrombus (cd-RVT) with pT3aN0M0 RCC. We retrospectively reviewed 91 patients with pT3aN0M0 RCC who underwent surgical treatment. Patients with tumor size > 7 cm, UCSI, three invasive sites (PFI + SFI + RVI), and cd-RVT showed a significant correlation with high recurrence rates (hazard ration (HR) 2.98, p = 0.013; HR 8.86, p < 0.0001; HR 14.28, p = 0.0008; and HR 4.08, p = 0.0074, respectively). In the multivariate analysis, tumor size of >7 cm, the presence of UCSI, and cd-RVT were the independent predictors of recurrence (HR 3.39, p = 0.043, HR 7.31, p = 0.01, HR 5.06, p = 0.018, respectively). In pT3a RCC, tumor size (7 cm cut-off), UCSI, and cd-RVT may help to provide an early diagnosis of recurrence.
A Maximum Entropy Method for the Prediction of Size Distributions
Authors: Metzig Cornelia , Colijn Caroline
Published: March 2020

We propose a method to derive the stationary size distributions of a system, and the degree distributions of networks, using maximisation of the Gibbs-Shannon entropy. We apply this to a preferential attachment-type algorithm for systems of constant size, which contains exit of balls and urns (or nodes and edges for the network case). Knowing mean size (degree) and turnover rate, the power law exponent and exponential cutoff can be derived. Our results are confirmed by simulations and by computation of exact probabilities. We also apply this entropy method to reproduce existing results like the Maxwell-Boltzmann distribution for the velocity of gas particles, the Barabasi-Albert model and multiplicative noise systems.
Multivariate and Multiscale Complexity of Long-Range Correlated Cardiovascular and Respiratory Variability Series
Authors: Martins Aurora , Pernice Riccardo , Amado Celestino , Rocha Ana Paula , Silva Maria Eduarda , Javorka Michal , Faes Luca
Published: March 2020

Assessing the dynamical complexity of biological time series represents an important topic with potential applications ranging from the characterization of physiological states and pathological conditions to the calculation of diagnostic parameters. In particular, cardiovascular time series exhibit a variability produced by different physiological control mechanisms coupled with each other, which take into account several variables and operate across multiple time scales that result in the coexistence of short term dynamics and long-range correlations. The most widely employed technique to evaluate the dynamical complexity of a time series at different time scales, the so-called multiscale entropy (MSE), has been proven to be unsuitable in the presence of short multivariate time series to be analyzed at long time scales. This work aims at overcoming these issues via the introduction of a new method for the assessment of the multiscale complexity of multivariate time series. The method first exploits vector autoregressive fractionally integrated (VARFI) models to yield a linear parametric representation of vector stochastic processes characterized by short- and long-range correlations. Then, it provides an analytical formulation, within the theory of state-space models, of how the VARFI parameters change when the processes are observed across multiple time scales, which is finally exploited to derive MSE measures relevant to the overall multivariate process or to one constituent scalar process. The proposed approach is applied on cardiovascular and respiratory time series to assess the complexity of the heart period, systolic arterial pressure and respiration variability measured in a group of healthy subjects during conditions of postural and mental stress. Our results document that the proposed methodology can detect physiologically meaningful multiscale patterns of complexity documented previously, but can also capture significant variations in complexity which cannot be observed using standard methods that do not take into account long-range correlations.
The Effect of Adhesive Additives on Silica Gel Water Sorption Properties
Authors: Sztekler Karol , Kalawa Wojciech , Mlonka-Medrala Agata , Nowak Wojciech , Mika Łukasz , Krzywanski Jaroslaw , Grabowska Karolina , Sosnowski Marcin , Debniak Marcin
Published: March 2020

Adsorption chillers are characterized by low electricity consumption, lack of moving parts, and high reliability. The disadvantage of these chillers is their large weight due to low adsorbent sorption capacity. Therefore, the attention is turned to finding a sorbent with a high water sorption capacity and enhanced thermal conductivity to increase chiller efficiency. The article discusses the impact of selected adhesives used for the production of an adsorption bed in order to improve heat exchange on its surface. Experiments with silica gel with three commercial types of glue on metal plates representing heat exchanger were performed. The structure of samples was observed under a microscope to determine the coverage of adsorbent by glue. To determine the kinetics of the free adsorption, the amounts of moisture adsorbed and the desorption dynamics the prepared samples of coated bed on metal plates were moisturized and dried in a moisture analyzer. Samples made of silica gel mixed with the adhesive 2-hydroxyethyl cellulose, show high adsorption capacity, low dynamic adsorption, and medium dynamic desorption. Samples containing adhesive poly(vinyl alcohol) adsorb less moisture, but free adsorption and desorption were more dynamic. Samples containing the adhesive hydroxyethyl cellulose show lower moisture capacity, relatively dynamic adsorption, and lower dynamic desorption.
Progress and Opportunities for Exsolution in Electrochemistry
Authors: Rosen Brian A.
Published: March 2020

This perspective gives the reader a broad overview of the progress that has been made in understanding the physics of the exsolution process and its exploitation in electrochemical devices in the last five years. On the basis of this progress, the community is encouraged to pursue unreported and under-reported opportunities for the advancement of exsolution in electrochemical applications through new materials discovery.
Cost Optimization of a Stand-Alone Hybrid Energy System with Fuel Cell and PV
Authors: Singh Shakti , Chauhan Prachi , Aftab Mohd Asim , Ali Ikbal , Hussain S. M. Suhail , Ustun Taha Selim
Published: March 2020

Renewable energy has become very popular in recent years. The amount of renewable generation has increased in both grid-connected and stand-alone systems. This is because it can provide clean energy in a cost-effective and environmentally friendly fashion. Among all varieties, photovoltaic (PV) is the ultimate rising star. Integration of other technologies with solar is enhancing the efficiency and reliability of the system. In this paper a fuel cell–solar photovoltaic (FC-PV)-based hybrid energy system has been proposed to meet the electrical load demand of a small community center in India. The system is developed with PV panels, fuel cell, an electrolyzer and hydrogen storage tank. Detailed mathematical modeling of this system as well as its operation algorithm have been presented. Furthermore, cost optimization has been performed to determine ratings of PV and Hydrogen system components. The objective is to minimize the levelized cost of electricity (LCOE) of this standalone system. This optimization is performed in HOMER software as well as another tool using an artificial bee colony (ABC). The results obtained by both methods have been compared in terms of cost effectiveness. It is evident from the results that for a 68 MWh/yr of electricity demand is met by the 129 kW Solar PV, 15 kW Fuel cell along with a 34 kW electrolyzer and a 20 kg hydrogen tank with a LPSP of 0.053%. The LCOE is found to be in 0.228 $/kWh. Results also show that use of more sophisticated algorithms such as ABC yields more optimized solutions than package programs, such as HOMER. Finally, operational details for FC-PV hybrid system using IEC 61850 inter-operable communication is presented. IEC 61850 information models for FC, electrolyzer, hydrogen tank were developed and relevent IEC 61850 message exchanges for energy management in FC-PV hybrid system are demonstrated.
Fault Investigation in Cascaded H-Bridge Multilevel Inverter through Fast Fourier Transform and Artificial Neural Network Approach
Authors: Kiran Kumar G. , Parimalasundar E. , Elangovan D. , Sanjeevikumar P. , Lannuzzo Francesco , Holm-Nielsen Jens Bo
Published: March 2020

In recent times, multilevel inverters are used as a high priority in many sizeable industrial drive applications. However, the reliability and performance of multilevel inverters are affected by the failure of power electronic switches. In this paper, the failure of power electronic switches of multilevel inverters is identified with the help of a high-performance diagnostic system during the open switch and low condition. Experimental and simulation analysis was carried out on five levels cascaded h-bridge multilevel inverter, and its output voltage waveforms were synthesized at different switch fault cases and different modulation index parameter values. Salient frequency-domain features of the output voltage signal were extracted using a Fast Fourier Transform decomposition technique. The real-time work of the proposed fault diagnostic system was implemented through the LabVIEW software. The Offline Artificial neural network was trained using the MATLAB software, and the overall system parameters were transferred to the LabVIEW real-time system. With the proposed method, it is possible to identify the individual faulty switch of multilevel inverters successfully.
T2FL: An Efficient Model for Wind Turbine Fatigue Damage Prediction for the Two-Turbine Case
Authors: Galinos Christos , Kazda Jonas , Lio Wai Hou , Giebel Gregor
Published: March 2020

Wind farm load assessment is typically conducted using Computational Fluid Dynamics (CFD) or aeroelastic simulations, which need a lot of computer power. A number of applications, for example wind farm layout optimisation, turbine lifetime estimation and wind farm control, requires a simplified but sufficiently detailed model for computing the turbine fatigue load. In addition, the effect of turbine curtailment is particularly important in the calculation of the turbine loads. Therefore, this paper develops a fast and computationally efficient method for wind turbine load assessment in a wind farm, including the wake effects. In particular, the turbine fatigue loads are computed using a surrogate model that is based on the turbine operating condition, for example, power set-point and turbine location, and the ambient wind inflow information. The Turbine to Farm Loads (T2FL) surrogate model is constructed based on a set of high fidelity aeroelastic simulations, including the Dynamic Wake Meandering model and an artificial neural network that uses the Bayesian Regularisation (BR) and Levenberg–Marquardt (LM) algorithms. An ensemble model is used that outperforms model predictions of the BR and LM algorithms independently. Furthermore, a case study of a two turbine wind farm is demonstrated, where the turbine power set-point and fatigue loads can be optimised based on the proposed surrogate model. The results show that the downstream turbine producing more power than the upstream turbine is favourable for minimising the load. In addition, simulation results further demonstrate that the accumulated fatigue damage of turbines can be effectively distributed amongst the turbines in a wind farm using the power curtailment and the proposed surrogate model.
Comparative Study of the Effective Release Energy, Residual Gas Fraction, and Emission Characteristics with Various Valve Port Diameter-Bore Ratios (VPD/B) of a Four-Stroke Spark Ignition Engine
Authors: Khoa Nguyen Xuan , Lim Ocktaeck
Published: March 2020

In this research, the residual gas, peak firing pressure increase, and effective release energy were completely investigated. To obtain this target, the experimental system is installed with a dynamo system and a simulation model was setup. Through combined experimental and simulation methods, the drawbacks of the hardware optimization method were eliminated. The results of the research show that the valve port diameter-bore ratio (VPD/B) has a significant effect on the residual gas, peak firing pressure increase, and effective release energy of a four-stroke spark ignition engine. In this research, the engine was performed at 3000 rpm and full load condition. Following increased IPD/B ratio of 0.3–0.5. The intake port and exhaust port diameter has a contrary effect on engine volumetric efficiency, the residual gas ratio increase 27.3% with larger intake port and decrease 18.6% with larger exhaust port. The engine will perform optimal thermal efficiency when the trapped residual gas fraction ratio is from 13% to 14%. The maximum effective release energy was 0.45 kJ at 0.4 intake port-bore ratio, and 0.451 kJ at 0.35 exhaust port-bore ratio. The NOx emission increases until achieved a maximum value after that decrease even VPD/B was still increasing. With a VPD/B ratio of 0.35 to 0.4, the engine works without the misfiring.
Quality Evaluation and Characterization of Specific Spoilage Organisms of Spanish Mackerel by High-Throughput Sequencing during 0 °C Cold Chain Logistics
Authors: Zheng Ruihang , Xu Xiaorong , Xing Jiali , Cheng Hai , Zhang Shufen , Shen Jian , Li Hesheng
Published: March 2020

Exploring the spoilage mechanism of Spanish mackerel is important to reduce the waste of Spanish mackerel and extend its shelf life. Cold chain logistics are commonly used to maintain the high quality and prolong the shelf life of aquatic products in circulation and storage. We assessed the sensory (body surface, odor, fish gills, fish elasticity, eyes, and overall assessment), chemical (total volatile base nitrogen (TVB-N), pH and 2-thiobarbituric acid (TBA)), and microbial characteristics (total viable counts (TVCs) and lactic acid bacteria) of Spanish mackerel combined with high-throughput sequencing at frequent intervals to determine their freshness and specific spoilage organisms (SSOs) during 0 °C cold chain logistics. Results showed that TVB-N, TBA, and TVCs correlated well (R2 > 0.90) with the sensory scores with prolonged circulation and storage time. The SSOs of Spanish mackerel were Proteobacteria in phylum and Pseudomonas in genus. The shelf life of mackerel under the 0 °C ice-stored cold chain system was approximately seven days, which is roughly three days longer compared with the traditional low-temperature storage method. These findings indicated that the freshness evaluation of Spanish mackerel in cold-chain circulation could be achieved by selecting appropriate chemical, microbial, and sensory indices. The study contributes to extend the shelf life of cold-chain Spanish mackerel by inhibiting the growth of dominant bacteria and provides a basis for the development of methods and tools to predict the shelf life of Spanish mackerel.
Research on the Relationship Between Safety Leadership, Safety Attitude and Safety Citizenship Behavior of Railway Employees
Authors: Li Mengjie , Zhai Huaiyuan , Zhang Junjie , Meng Xiangcheng
Published: March 2020

The daily operation and maintenance work of railways are very dangerous. Railway employees often have safety accidents while working, and the safety citizenship behavior (SCB) of railway employees can effectively reduce the accident rate. Therefore, it is of great significance to identify the main safety constructs affecting the SCB of railway employees to minimize accidents. This paper puts forward a supposed model of the influence mechanism of safety leadership (SL) on employee SCB through the mediation of safety attitude (SA). A questionnaire was used with railway employees, and 238 valid responses were finally collected. A structural equation model (SEM) was used to explore the relationship between SL, SA and SCB. The results showed the SL is positively related to the SA, and it can further promote the SCB of railway employees. In addition, SA has a positive impact on employee SCB.
Minecraft as a Tool for Engaging Children in Urban Planning: A Case Study in Tirol Town, Brazil
Authors: de Andrade Bruno , Poplin Alenka , Sousa de Sena Ítalo
Published: March 2020

The purpose of this paper is to explore the potential of Minecraft’s game environment for urban planning with older and younger children in a public school in Tirol town, Brazil. Minecraft is employed as an innovative tool to tackle the present lack of engagement and involvement of key societal actors such as children and young people in urban planning. Thus, how can games support children to co-design their future city? Which heritage values do they represent graphically in the game environment? Geogames are games that provide a visualization of a real spatial context and in this study, Minecraft is the tool which we use to explore youth engagement. We designed two experiments, which tested Minecraft as a geogame environment for engaging young people in urban planning. These experiments were conducted with children, who emerged as active emancipated actors to bring their values to the planning practice. The playtesting results revealed the potential of Minecraft to keep children engaged in the design workshop, as well as their relevant ludic ability to co-create walkable, green, and interactive places. New research questions arose about the potential of creating a culture of planning among children in order to motivate other social actors to share responsibilities for sustainable development and management.
Novel Molecular Mechanisms of Gangliosides in the Nervous System Elucidated by Genetic Engineering
Authors: Furukawa Koichi , Ohmi Yuhsuke , Yesmin Farhana , Tajima Orie , Kondo Yuji , Zhang Pu , Hashimoto Noboru , Ohkawa Yuki , Bhuiyan Robiul H. , Furukawa Keiko
Published: March 2020

Acidic glycosphingolipids, i.e., gangliosides, are predominantly and consistently expressed in nervous tissues of vertebrates at high levels. Therefore, they are considered to be involved in the development and function of nervous systems. Recent studies involving genetic engineering of glycosyltransferase genes have revealed novel aspects of the roles of gangliosides in the regulation of nervous tissues. In this review, novel findings regarding ganglioside functions and their modes of action elucidated mainly by studies of gene knockout mice are summarized. In particular, the roles of gangliosides in the regulation of lipid rafts to maintain the integrity of nervous systems are reported with a focus on the roles in the regulation of neuro-inflammation and neurodegeneration via complement systems. In addition, recent advances in studies of congenital neurological disorders due to genetic mutations of ganglioside synthase genes and also in the techniques for the analysis of ganglioside functions are introduced.
Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis
Authors: Sumida Yoshio , Yoneda Masashi , Tokushige Katsutoshi , Kawanaka Miwa , Fujii Hideki , Yoneda Masato , Imajo Kento , Takahashi Hirokazu , Eguchi Yuichiro , Ono Masafumi , Nozaki Yuichi , Hyogo Hideyuki , Koseki Masahiro , Yoshida Yuichi , Kawaguchi Takumi , Kamada Yoshihiro , Okanoue Takeshi , Nakajima Atsushi ,   Japan Study Group of NAFLD (JSG-NAFLD)
Published: March 2020

Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D is closely associated with nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D have extensively been established, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D.
Comparative Transcriptome-Based Mining and Expression Profiling of Transcription Factors Related to Cold Tolerance in Peanut
Authors: Jiang Chunji , Zhang He , Ren Jingyao , Dong Jiale , Zhao Xinhua , Wang Xiaoguang , Wang Jing , Zhong Chao , Zhao Shuli , Liu Xibo , Gao Shibo , Yu Haiqiu
Published: March 2020

Plants tolerate cold stress by regulating gene networks controlling cellular and physiological traits to modify growth and development. Transcription factor (TF)-directed regulation of transcription within these gene networks is key to eliciting appropriate responses. Identifying TFs related to cold tolerance contributes to cold-tolerant crop breeding. In this study, a comparative transcriptome analysis was carried out to investigate global gene expression of entire TFs in two peanut varieties with different cold-tolerant abilities. A total of 87 TF families including 2328 TF genes were identified. Among them, 445 TF genes were significantly differentially expressed in two peanut varieties under cold stress. The TF families represented by the largest numbers of differentially expressed members were bHLH (basic helix—loop—helix protein), C2H2 (Cys2/His2 zinc finger protein), ERF (ethylene-responsive factor), MYB (v-myb avian myeloblastosis viral oncogene homolog), NAC (NAM, ATAF1/2, CUC2) and WRKY TFs. Phylogenetic evolutionary analysis, temporal expression profiling, protein–protein interaction (PPI) network, and functional enrichment of differentially expressed TFs revealed the importance of plant hormone signal transduction and plant-pathogen interaction pathways and their possible mechanism in peanut cold tolerance. This study contributes to a better understanding of the complex mechanism of TFs in response to cold stress in peanut and provides valuable resources for the investigation of evolutionary history and biological functions of peanut TFs genes involved in cold tolerance.
Identification of Novel Genomic Regions and Superior Alleles Associated with Zn Accumulation in Wheat Using a Genome-Wide Association Analysis Method
Authors: Zhou Zhengfu , Shi Xia , Zhao Ganqing , Qin Maomao , Ibba Maria Itria , Wang Yahuan , Li Wenxu , Yang Pan , Wu Zhengqing , Lei Zhensheng , Wang Jiansheng
Published: March 2020

Micronutrient deficiencies, and especially zinc (Zn) deficiency, pose serious health problems to people who mainly depend on cereal-based diets. Here, we performed a genome-wide association study (GWAS) to detect the genetic basis of the Zn accumulation in wheat (Triticum aestivum L.) grains with a diversity panel of 207 bread wheat varieties. To uncover authentic quantitative trait loci (QTL) controlling Zn accumulation, the varieties were planted in three locations. In total, 29 unique loci associated with Zn grain accumulation were identified. Notably, seven non-redundant loci located on chromosomes 1B, 3B, 3D, 4A, 5A, 5B, and 7A, were detected at least in two environments. Of these quantitative trait loci (QTL), six coincided with known QTL or genes, whereas the highest effect QTL on chromosome 3D identified in this study was not reported previously. Searches of public databases revealed that the seven identified QTL coincided with seven putative candidate genes linked to Zn accumulation. Among these seven genes, NAC domain-containing protein gene (TraesCS3D02G078500) linked with the most significant single nucleotide polymorphism (SNP) AX-94729264 on chromosome 3D was relevant to metal accumulation in wheat grains. Results of this study provide new insights into the genetic architecture of Zn accumulation in wheat grains.
FASN Is a Biomarker Enriched in Malignant Glioma-Derived Extracellular Vesicles
Authors: Ricklefs Franz L. , Maire Cecile L. , Matschke Jakob , Dührsen Lasse , Sauvigny Thomas , Holz Mareike , Kolbe Katharina , Peine Sven , Herold-Mende Christel , Carter Bob , Chiocca E. Antonio , Lawler Sean E. , Westphal Manfred , Lamszus Katrin
Published: March 2020

Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.
STAT3 for Cardiac Regenerative Medicine: Involvement in Stem Cell Biology, Pathophysiology, and Bioengineering
Authors: Nakao Shu , Tsukamoto Tasuku , Ueyama Tomoe , Kawamura Teruhisa
Published: March 2020

Heart disease is the most common cause of death in developed countries, but the medical treatments for heart failure remain limited. In this context, the development of cardiac regeneration therapy for severe heart failure is important. Owing to their unique characteristics, including multiple differentiation and infinitive self-renewal, pluripotent stem cells can be considered as a novel source for regenerative medicine. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling plays critical roles in the induction, maintenance, and differentiation of pluripotent stem cells. In the heart, JAK/STAT3 signaling has diverse cellular functions, including myocardial differentiation, cell cycle re-entry of matured myocyte after injury, and anti-apoptosis in pathological conditions. Therefore, regulating STAT3 activity has great potential as a strategy of cardiac regeneration therapy. In this review, we summarize the current understanding of STAT3, focusing on stem cell biology and pathophysiology, as they contribute to cardiac regeneration therapy. We also introduce a recently reported therapeutic strategy for myocardial regeneration that uses engineered artificial receptors that trigger endogenous STAT3 signal activation.
Involvement of Salicylic Acid and Other Phenolic Compounds in Light-Dependent Cold Acclimation in Maize
Authors: Pál Magda , Janda Tibor , Majláth Imre , Szalai Gabriella
Published: March 2020

The exposure of plants to non-lethal low temperatures may increase their tolerance to a subsequent severe chilling stress. To some extent, this is also true for cold-sensitive species, including maize. In the present work, based on our previous microarray experiment, the differentially expressed genes with phenylpropanoid pathways in the focus were further investigated in relation to changes in certain phenolic compounds and other plant growth regulators. Phenylalanine ammonia lyase (PAL) was mainly activated under limited light conditions. However, light-induced anthocyanin accumulation occurred both in the leaves and roots. Chilling stress induced the accumulation of salicylic acid (SA), but this accumulation was moderated in the cold-acclimated plants. Acclimation also reduced the accumulation of jasmonic acid (JA) in the leaves, which was rather induced in the roots. The level of abscisic acid (ABA) is mainly related to the level of the stress, and less indicated the level of the acclimation. The highest glutathione (GSH) amount was observed during the recovery period in the leaves of plants that were cold acclimated at growth light, while their precursors started to accumulate GSH even during the chilling. In conclusion, different light conditions during the cold acclimation period differentially affected certain stress-related mechanisms in young maize plants and changes were also light-dependent in the root, not only in the leaves.
Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu
Authors: Toncic Ruzica Jurakic , Jakasa Ivone , Hadzavdic Suzana Ljubojevic , Goorden Susan MI , Vlugt Karen JM Ghauharali-van der , Stet Femke S , Balic Anamaria , Petkovic Mikela , Pavicic Borna , Zuzul Kristina , Marinovic Branka , Kezic Sanja
Published: March 2020

Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18–0.61), 0.56 (IQR 0.32–0.76) and 19.32 (IQR 7.86–27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = −0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes.
An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity
Authors: Efthymakis Konstantinos , Clemente Emanuela , Marchioni Michele , Di Nicola Marta , Neri Matteo , Sallese Michele
Published: March 2020

Non-celiac wheat sensitivity (NCWS) is a recently recognized syndrome triggered by a gluten-containing diet. The pathophysiological mechanisms engaged in NCWS are poorly understood and, in the absence of laboratory markers, the diagnosis relies only on a double-blind protocol of symptoms evaluation during a gluten challenge. We aimed to shed light on the molecular mechanisms governing this disorder and identify biomarkers helpful to the diagnosis. By a genome-wide transcriptomic analysis, we investigated gene expression profiles of the intestinal mucosa of 12 NCWS patients, as well as 7 controls. We identified 300 RNA transcripts whose expression differed between NCWS patients and controls. Only 37% of these transcripts were protein-coding RNA, whereas the remaining were non-coding RNA. Principal component analysis (PCA) and receiver operating characteristic curves showed that these microarray data are potentially useful to set apart NCWS from controls. Literature and network analyses indicated a possible implication/dysregulation of innate immune response, hedgehog pathway, and circadian rhythm in NCWS. This exploratory study indicates that NCWS can be genetically defined and gene expression profiling might be a suitable tool to support the diagnosis. The dysregulated genes suggest that NCWS may result from a deranged immune response. Furthermore, non-coding RNA might play an important role in the pathogenesis of NCWS.
The Control of Developmental Phase Transitions by microRNAs and Their Targets in Seed Plants
Authors: Ma Jingyi , Zhao Pan , Liu Shibiao , Yang Qi , Guo Huihong
Published: March 2020

Seed plants usually undergo various developmental phase transitions throughout their lifespan, mainly including juvenile-to-adult and vegetative-to-reproductive transitions, as well as developmental transitions within organ/tissue formation. MicroRNAs (miRNAs), as a class of small endogenous non-coding RNAs, are involved in the developmental phase transitions in plants by negatively regulating the expression of their target genes at the post-transcriptional level. In recent years, cumulative evidence has revealed that five miRNAs, miR156, miR159, miR166, miR172, and miR396, are key regulators of developmental phase transitions in plants. In this review, the advanced progress of the five miRNAs and their targets in regulating plant developmental transitions, especially in storage organ formation, are summarized and discussed, combining our own findings with the literature. In general, the functions of the five miRNAs and their targets are relatively conserved, but their functional divergences also emerge to some extent. In addition, potential research directions of miRNAs in regulating plant developmental phase transitions are prospected.
Disorders of Puberty: Endocrinology of the Pre-Pubertal Testis
Authors: La Vignera Sandro , Cannarella Rossella , Condorelli Rosita A. , Calogero Aldo E.
Published: March 2020

Male infertility is a widespread condition among western countries. Meta-regression data show that sperm concentration and total sperm count have halved in the last decades. The reasons of this decline are still unclear. The evaluation of testicular function in pre-pubertal children may be effective in the timely detection of Sertoli cell (SC) disfunction, which anticipates the diagnosis of male infertility. The aim of this Special Issue is to gather together in vitro evidence on SC physiology, causes of SC dysfunction, and to suggest a practical approach to be adopted in children.
Silicate Sawing Sludge Recovery in Thermo Eco-Mortar for Macroporous Plaster
Authors: Zichella Lorena , Marone Paolo , Buonanno Pasquale , D’Amore Marco , Bellopede Rossana
Published: March 2020

The aim of this research was to develop a new eco-product to find a correct recovery of silicate sawing sludge by means of waste management according to European criteria. To reach this goal, a thermal eco-mortar for a macroporous plaster was developed. The main characteristics of a plaster that influence the correct choice of the mortar are good adherence with underlying support, impermeability, thermal and acoustic insulation, mechanical resistance and ability to allow transpiration processes through the wall’s perimeters. Plaster is a mortar composed of a binding part that incorporates sand with a selected particle size distribution, not greater than 2 mm. The sludge, to be used as plaster, must satisfy requirements related to thermal insulation, resistance to moisture, mechanical resistance and good injection. For this purpose, low-content metals sludge, derived from the Luserna stone flaming and cutting slabs, are to be reused as a substitute for the sands and fine particles, respectively, that are normally used to produce plasters. The laboratory tests carried out on the finished product, in accordance with European standards, are as follows: water absorption, specific density, flexural and compressive strength, before and after freeze and thaw cycles, pull out, salt crystallisation cycle resistance and thermal conductivity. Chemical and leaching tests were carried out to verify the possible release of heavy metals into the environment after installation. The product quality was demonstrated as the cement mortars, incorporating the metals, did not allow their release in nature. A sludge recovery, in an unaltered state, was provided to reduce any costs connected to a pre-treatment and to make recovery economically advantageous for the stone sector.
Effects of Ion Beam Etching on the Nanoscale Damage Precursor Evolution of Fused Silica
Authors: Zhong Yaoyu , Dai Yifan , Shi Feng , Song Ci , Tian Ye , Lin Zhifan , Zhang Wanli , Shen Yongxiang
Published: March 2020

Nanoscale laser damage precursors generated from fabrication have emerged as a new bottleneck that limits the laser damage resistance improvement of fused silica optics. In this paper, ion beam etching (IBE) technology is performed to investigate the evolutions of some nanoscale damage precursors (such as contamination and chemical structural defects) in different ion beam etched depths. Surface material structure analyses and laser damage resistance measurements are conducted. The results reveal that IBE has an evident cleaning effect on surfaces. Impurity contamination beneath the polishing redeposition layer can be mitigated through IBE. Chemical structural defects can be significantly reduced, and surface densification is weakened after IBE without damaging the precision of the fused silica surface. The photothermal absorption on the fused silica surface can be decreased by 41.2%, and the laser-induced damage threshold can be raised by 15.2% after IBE at 250 nm. This work serves as an important reference for characterizing nanoscale damage precursors and using IBE technology to increase the laser damage resistance of fused silica optics.
Mechanical Properties of Monolayer MoS2 with Randomly Distributed Defects
Authors: Akhter Mohammed Javeed , Kuś Wacław , Mrozek Adam , Burczyński Tadeusz
Published: March 2020

The variation of elastic constants stiffness coefficients with respect to different percentage ratios of defects in monolayer molybdenum disulfide (MLMoS2) is reported for a particular set of atomistic nanostructural characteristics. The common method suggested is to use conventional defects such as single vacancy or di vacancy, and the recent studies use stone-walled multiple defects for highlighting the differences in the mechanical and electronic properties of 2D materials. Modeling the size influence of monolayer MoS2 by generating defects which are randomly distributed for a different percentage from 0% to 25% is considered in the paper. In this work, the geometry of the monolayer MoS2 defects modeled as randomized over the domain are taken into account. For simulation, the molecular static method is adopted and study the effect of elastic stiffness parameters of the 2D MoS2 material. Our findings reveals that the expansion of defects concentration leads to a decrease in the elastic properties, the sheer decrease in the elastic properties is found at 25%. We also study the diffusion of Molybdenum (Mo) in Sulphur (S) layers of atoms within MoS2 with Mo antisite defects. The elastic constants dwindle in the case of antisite defects too, but when compared to pure defects, the reduction was to a smaller extent in monolayer MoS2. Nevertheless, the Mo diffusion in sulfur gets to be more and more isotropic with the increase in the defect concentrations and elastic stiffness decreases with antisite defects concentration up to 25%. The distribution of antisite defects plays a vital role in modulating Mo diffusion in sulfur. These results will be helpful and give insights in the design of 2D materials.
GSTP1 rs1138272 Polymorphism Affects Prostate Cancer Risk
Authors: Santric Veljko , Djokic Milica , Suvakov Sonja , Pljesa-Ercegovac Marija , Nikitovic Marina , Radic Tanja , Acimovic Miodrag , Stankovic Vesna , Bumbasirevic Uros , Milojevic Bogomir , Babic Uros , Dzamic Zoran , Simic Tatjana , Dragicevic Dejan , Savic-Radojevic Ana
Published: March 2020

Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89–8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19–2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56–11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55–8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05–44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene–gene interactions in human susceptibility to this cancer.
The Effect of Hydrogen on Pore Formation in Aluminum Alloy Castings: Myth Versus Reality
Authors: Tiryakioğlu Murat
Published: March 2020

The solubility of hydrogen in liquid and solid aluminum is reviewed. Based on classical nucleation theory, it is shown that pores cannot nucleate either homogeneously or heterogeneously in liquid aluminum. Results of in situ studies on pore formation show that pores appear at low hydrogen supersaturation levels, bypassing nucleation completely. The results are explained based on the bifilm theory introduced by Prof. John Campbell, as this theory is currently the most appropriate, and most likely, the only mechanism for pores to form. Examples for the effect of hydrogen on pore formation are given by using extreme data from the literature. It is concluded that a fundamental change in how hydrogen is viewed is needed in aluminum casting industry.