bluuebunny/crossref_metadata_2025 huggingface dataset:
A Stochastic Planning Model for Battery Energy Storage Systems Coupled with Utility-Scale Solar Photovoltaics
Authors: Park Heejung
Published: February 2021

With recent technology advances and price drop, battery energy storage systems (BESSs) are considered as a promising storage technology in power systems. In this paper, a stochastic BESS planning model is introduced, which determines optimal capacity and durations of BESSs to co-locate utility-scale solar photovoltaic (PV) systems in a high-voltage power system under the uncertainties of renewable resources and electric load. The optimization model minimizing total costs aims to obtain at least 20% electric energy from renewable sources, while satisfying all the physical constraints. Furthermore, two-stage stochastic programming is applied to formulate mathematical optimization problem to find out optimal durations and capacity of BESSs. In scheduling BESSs, chronology needs to be considered to represent temporal changes of BESS states; therefore, a scenario generation method to generate random sample paths with 1-h time step is adopted to explicitly represent uncertainty and temporal changes. The proposed mathematical model is applied to a modified IEEE 300-bus system that comprises 300 electric buses and 411 transmission lines. Optimal BESS durations and capacity are compared when different numbers of scenarios are employed to see the sensitivity to the number of scenarios in the model, and “value of stochastic solution” (VSS) is calculated to verify the impacts of inclusion of stochastic parameters. The results show that the building costs and capacity of BESSs increase when the number of scenarios increases from 10 to 30. By inspecting VSSs, it is observed that an explicit representation of stochastic parameters affects the optimal value, and the impacts become larger when the larger number of scenarios are applied.
Multi-Objective Optimization of a Hybrid Nanogrid/Microgrid: Application to Desert Camps in Hafr Al-Batin
Authors: Bouchekara Houssem Rafik Al-Hana , Shahriar Mohammad Shoaib , Javaid Muhammad Sharjeel , Sha’aban Yusuf Abubakar , Ramli Makbul Anwari Muhammad
Published: February 2021

This paper presents an optimal design for a nanogrid/microgrid for desert camps in the city of Hafr Al-Batin in Saudi Arabia. The camps were designed to operate as separate nanogrids or to operate as an interconnected microgrid. The hybrid nanogrid/microgrid considered in this paper consists of a solar system, storage batteries, diesel generators, inverter, and load components. To offer the designer/operator various choices, the problem was formulated as a multi-objective optimization problem considering two objective functions, namely: the cost of electricity (COE) and the loss of power supply probability (LPSP). Furthermore, various component models were implemented, which offer a variety of equipment compilation possibilities. The formulated problem was then solved using the multi-objective evolutionary algorithm, based on both dominance and decomposition (MOEA/DD). Two cases were investigated corresponding to the two proposed modes of operation, i.e., nanogrid operation mode and microgrid operation mode. The microgrid was designed considering the interconnection of four nanogrids. The obtained Pareto front (PF) was reported for each case and the solutions forming this front were discussed. Based on this investigation, the designer/operator can select the most appropriate solution from the available set of solutions using his experience and other factors, e.g., budget, availability of equipment and customer-specific requirements. Furthermore, to assess the quality of the solutions found using the MOEA/DD, three different methods were used, and their results compared with the MOEA/DD. It was found that the MOEA/DD obtained better results (nondominated solutions), especially for the microgrid operation mode.
Sensory Acceptability and Proximate Composition of 3-Blend Plant-Based Dairy Alternatives
Authors: Oduro Ama Frempomaa , Saalia Firibu Kwesi , Adjei Maame Yaakwaah Blay
Published: February 2021

Limitations of plant-based dairy alternatives as sustainable foods are their relatively low protein content and low sensory appeal. In this study, we used a consumer-led product development approach to improve the sensory appeal of existing prototypes of 3-blend dairy alternatives produced from melon seeds, peanuts and coconut. We used Relative Preference Mapping (RPM) and consumer acceptance testing using the 9-point hedonic scale to respectively identify innovative flavours and deduce the effect of ingredient components on consumer sensory appeal. Mixture design was used as the formulation tool to obtain optimized prototypes of the 3-blend dairy alternatives. Proximate analysis of the new prototypes, instrumental color assessment and consumer testing provided a basis to select a sustainable 3-blend dairy alternative. This prototype had a relatively high protein content (2.16%), was considered innovative by target consumers and also had a moderate liking score (6.55 ± 1.88) on the 9-point hedonic scale. Prototypes with higher protein content had low sensory appeal and were not considered innovative. Other prototypes with innovative sensory appeal had low protein content. By combining different plant raw materials and utilizing different sensory testing methods, we were able to design sustainable plant-based dairy alternatives which can be further optimized.
State-of-the-Art of Analytical Techniques to Determine Food Fraud in Olive Oils
Authors: González-Pereira Antia , Otero Paz , Fraga-Corral Maria , Garcia-Oliveira Paula , Carpena Maria , Prieto Miguel A. , Simal-Gandara Jesus
Published: February 2021

The benefits of the food industry compared to other sectors are much lower, which is why producers are tempted to commit fraud. Although it is a bad practice committed with a wide variety of foods, it is worth noting the case of olive oil because it is a product of great value and with a high percentage of fraud. It is for all these reasons that the authenticity of olive oil has become a major problem for producers, consumers, and legislators. To avoid such fraud, it is necessary to develop analytical techniques to detect them. In this review, we performed a complete analysis about the available instrumentation used in olive fraud which comprised spectroscopic and spectrometric methodology and analyte separation techniques such as liquid chromatography and gas chromatography. Additionally, other methodology including protein-based biomolecular techniques and analytical approaches like metabolomic, hhyperspectral imaging and chemometrics are discussed.
Assessment of Antimicrobial Activity of Pomegranate, Cranberry, and Black Chokeberry Extracts against Foodborne Pathogens
Authors: Daoutidou Maria , Plessas Stavros , Alexopoulos Athanasios , Mantzourani Ioanna
Published: February 2021

Herbal and plant extracts are being applied to a wide range of foods against different types of foodborne pathogens. In the present study, ethanolic and aqueous extracts of different concentrations (5% v/v, 10% v/v, and 20% v/v) from cranberry (Vaccinium macrocarpon), black chokeberry (Aronia melanocarpa), and pomegranate (Punica granatum L.) plants were applied in five concentrations (62.5 to 1000 mg/mL) against foodborne strains of Staphylococcus aureus, Escherichia coli, and Streptococcus pyogenes. The results revealed that a low concentration of solvents (5% v/v) did not exhibit decreased antimicrobial activity in comparison with higher solvent concentrations (10% and 20% v/v). Additionally, both aqueous and ethanolic extracts were highly effective against pathogens even in their low concentrations (62.5 mg/mL and 125 mg/mL). Likewise, the extracts exhibited promising results (aqueous extracts of pomegranate, cranberry, and black chokeberry in a food-compatible concentration of 2% w/v) were applied to raw pork meatball production, and their antimicrobial activity was recorded versus Enterobacteriaceae, total mesophilic bacteria (TMB), lactic acid bacteria (LAB), Staphylococcus spp., Pseudomonas spp., and yeasts/molds. The outcome demonstrated that meatballs that contained aqueous extracts of pomegranate were more resistant to spoilage compared to all of the other samples, as it was preserved for more days. Likewise, these extracts of a plant origin could be used as natural preservatives in meat products, even in their low concentrations.
Investigating Australian Consumers’ Perceptions of and Preferences for Different Styles of Sparkling Wine Using the Fine Wine Instrument
Authors: Verdonk Naomi , Ristic Renata , Culbert Julie A. , Pearce Karma , Wilkinson Kerry L.
Published: February 2021

This study investigated consumer preferences for different styles of sparkling wine and the influence of wine style and occasion on sparkling wine purchasing and consumption behavior. Australian consumers (n = 203) completed an online survey and blind tasting of representative styles of commercial sparkling wines, including Champagne. Wine sensory profiles were determined by descriptive analysis using a trained panel (n = 12) and consumers were segmented into ‘No Frills’, ‘Aspirant’ and ‘Enthusiast’ clusters using the Fine Wine Instrument. Consumer perceptions, preferences and liking were measured using 9-point hedonic scales and compared via statistical analysis. Consumers anticipated liking Champagne and sparkling white wine the most, and Moscato and Prosecco the least, but on tasting, could only readily identify the Moscato and sparkling red wines, as the most contrasting wine styles. As such, liking scores for the Champagne and sparkling white wine were significantly lower based on tasting (median scores were 6.0, compared with 9.0 and 8.0 for survey responses, respectively). Consumers’ preconceived expectations of different sparkling wine styles clearly influenced purchasing and consumption behavior. Aspirants and Enthusiasts were more likely to spend more per bottle for Champagne and sparkling white wine, and consumption of these sparkling wines was most frequently associated with celebratory occasions, such as anniversaries, birthdays, Christmas, New Year and weddings.
Volatile Compounds, Odour and Flavour Attributes of Lamb Meat from the Navarra Breed as Affected by Ageing
Authors: Insausti Kizkitza , Murillo-Arbizu María T. , Urrutia Olaia , Mendizabal José A. , Beriain María J. , Colle Michael J. , Bass Phillip D. , Arana Ana
Published: February 2021

This study aimed to assess the influence of ageing on the volatile compounds, as well as odour and flavour attributes of lamb meat from the Navarra breed. Twenty-one male lambs were fed a commercial concentrate diet after weaning and were harvested at 101 ± 6.5 days of age. From the Longissimus thoracis, 26 volatile compounds were identified, with hexanal, 2-propanone, and nonanal the most abundant (57.17% relative percentage abundance, RPA). The effect of ageing (1 vs. 4 d) was observed (p < 0.05) in six compounds: 1,4-dimethylbenzene decreased with ageing, while tridecane, 3-methylbutanal, 2-heptanone, 3-octanone, and 1-octen-3-ol increased. In general, ageing was linked to a decrease in livery and bloody flavour, bloody odour and ethanal, and an increase in pentane, hexanal, and heptanal, which are usually associated with fresh green grass and fat descriptors. Consequently, ageing lamb from the Navarra breed for four days might have a positive effect on meat sensory odour and flavour quality.
Using Einkorn and Tritordeum Brewers’ Spent Grain to Increase the Nutritional Potential of Durum Wheat Pasta
Authors: Nocente Francesca , Natale Chiara , Galassi Elena , Taddei Federica , Gazza Laura
Published: February 2021

Brewers’ spent grain (BSG), the major by-product of the brewing industry, can be used as a functional ingredient to increase the nutritional value of cereal-based products. In this work, micronized BSG from the einkorn and tritordeum brewing processes were characterized and used to produce four macaroni pasta formulations enriched with BSG at ratios of 5 g and 10 g/100 g of semolina. Einkorn BSG showed the highest values for all the parameters analyzed—proteins, total dietary fiber (TDF) and total antioxidant capacity (TAC)—except for β-glucan. TDF increased up to 42 and 68% in pasta samples enriched with 10% of BSG from tritordeum and einkorn, respectively. The replacement of 10% of semolina with BSG from both cereals significantly increased the β-glucan content and TAC values. Finally, the addition of BSG from einkorn and tritordeum affected to a minimal extent the sensory properties of cooked pasta, which showed higher values of optimal cooking time and cooking loss, but lower total organic matter compared to semolina pasta. Results from the sensorial judgment fell in the good quality ranges for durum wheat pasta; the incorporation of 10% of einkorn BSG resulted in the best compromise in terms of technological, nutritional and sensorial aspects of enriched pasta.
Development of Structured Sunflower Oil Systems for Decreasing Trans and Saturated Fatty Acid Content in Bakery Creams
Authors: Espert María , Sanz Teresa , Salvador Ana
Published: February 2021

In this work, the design of low moisture (10%) oil/water emulsions based on sunflower oil were investigated, as well as their application in a bakery cream as a conventional fat replacer. The emulsions were dehydrated to reach 10% moisture content, achieving highly concentrated vegetable oil gel emulsions of different consistencies and qualities. Physical properties of the dried emulsions were evaluated by texture, microstructure, and oil loss determination. The reformulated bakery creams with the dried emulsions obtained from 47% oil showed better spreadability, viscosity, and viscoelasticity properties. A shortening replacement with the dried emulsion obtained from 70% initial oil caused a negative impact on the creams’ consistency, with lower viscosity and lower hysteresis area, revealing a weakness of structure. This research provided new knowledge about the structuration of vegetable oils through concentrated emulsions and their application as a source of healthy fat in creams for bakery applications.
IPEX Syndrome: Genetics and Treatment Options
Authors: Ben-Skowronek Iwona
Published: February 2021

(1) Background: IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome characterizes a complex autoimmune reaction beginning in the perinatal period, caused by a dysfunction of the transcription factor forkhead box P3 (FOXP3). (2) Objectives: Studies have shown the clinical, immunological, and molecular heterogeneity of patients with IPEX syndrome. The symptoms, treatment, and survival were closely connected to the genotype of the IPEX syndrome. Recognition of the kind of mutation is important for the diagnostics of IPEX syndrome in newborns and young infants, as well as in prenatal screening. The method of choice for treatment is hematopoietic stem cell transplantation and immunosuppressive therapy. In children, supportive therapy for refractory diarrhea is very important, as well as replacement therapy of diabetes mellitus type 1 (DMT1) and other endocrinopathies. In the future, genetic engineering methods may be of use in the successful treatment of IPEX syndrome. (3) Conclusions: The genetic defects determine a diagnostic approach and prognosis, making the knowledge of the genetics of IPEX syndrome fundamental to introducing novel treatment methods.
Complete Mitochondrial DNA Genome of Nine Species of Sharks and Rays and Their Phylogenetic Placement among Modern Elasmobranchs
Authors: Kousteni Vasiliki , Mazzoleni Sofia , Vasileiadou Katerina , Rovatsos Michail
Published: February 2021

Chondrichthyes occupy a key position in the phylogeny of vertebrates. The complete sequence of the mitochondrial genome (mitogenome) of four species of sharks and five species of rays was obtained by whole genome sequencing (DNA-seq) in the Illumina HiSeq2500 platform. The arrangement and features of the genes in the assembled mitogenomes were identical to those found in vertebrates. Both Maximum Likelihood (ML) and Bayesian Inference (BI) analyses were used to reconstruct the phylogenetic relationships among 172 species (including 163 mitogenomes retrieved from GenBank) based on the concatenated dataset of 13 individual protein coding genes. Both ML and BI analyses did not support the “Hypnosqualea” hypothesis and confirmed the monophyly of sharks and rays. The broad notion in shark phylogeny, namely the division of sharks into Galeomorphii and Squalomorphii and the monophyly of the eight shark orders, was also supported. The phylogenetic placement of all nine species sequenced in this study produced high statistical support values. The present study expands our knowledge on the systematics, genetic differentiation, and conservation genetics of the species studied, and contributes to our understanding of the evolutionary history of Chondrichthyes.
Determinants of Travel Participation and Experiences of Wheelchair Users Traveling to the Bodrum Region: A Qualitative Study
Authors: Özcan Ezgi , Güçhan Topcu Zehra Güçhan , Arasli Hüseyin
Published: February 2021

Although the number of people with disabilities and types of disability increases day by day, a sufficient point has not been reached regarding accessible tourism. The participation rate of people with disabilities (PWDS) in tourism activities is low, and there is a big gap in the travel and accommodation sector in this regard. Studies of previous scholars have concluded that the accessible tourism market is a significant and profitable area, but determinants of participation to travel and process of travel, such as wheelchair user expectations, are consistently ignored by the tourism industry. The main purpose of this study is to determine the determinants of travel by examining the motivations, expectations, processes and experiences of PWDS using wheelchairs to participate in tourism. Research was performed in Turkey’s Bodrum district; 25 wheelchair users were included in the study. The keywords that emerged in the theoretical framework in light of the answers given to 39 open-ended questions online were coded in the Nvivo program. The results showed that wheelchair users intended to go on vacation but were less motivated to participate due to the lack of travel conditions. Wheelchair travelers argued that a companion was required for an enjoyable holiday that could meet their needs. In addition, the results revealed that the types of wheelchairs used by disabled passengers differ. The disabled stated that the wheelchairs they use in daily life are not suitable for use on the beach, sand or water. Despite the economic, social and technological change opportunities, basic tourism service expectations of PWDS are not met. This research project is a comprehensive study that makes determinations in terms of examining the social status of disabled people in terms of social sciences, examining the place and importance of disabled tourists in the market and eliminating the deficiencies of facilities serving in tourism.
The Impact of the Accuracy of Terrain Surface Data on the Navigation of Off-Road Vehicles
Authors: Rada Josef , Rybansky Marian , Dohnal Filip
Published: February 2021

Current soil and surface data are not detailed enough to obtain accurate analyses of cross-country movement. The reason for the research presented in this article was the absence of a methodology for the synthetic assessment of the influence of the terrain surface on the movement of military vehicles. The study is based on analyses of data and information sources of soils and surface conditions primarily with the aim to determine their reliability, availability and precision when used for analyses of terrain traversability by off-road vehicles. The key method to achieve the set objective is the employment of tractive charts of military vehicles and utilized coefficients, the coefficient of rolling resistance and the coefficient of adhesion. Input data and information is tested with a comparative method of cross-country movement analyses. Conversion of soil and surface types to tractive chart coefficients is currently not optimal. For the most part, evaluation of soil type is very inaccurate with a wide range of possible values. Results of the analysis propose developing a methodology of evaluating surface and soils for vehicle traversability.
TouchTerrain—3D Printable Terrain Models
Authors: Harding Chris , Hasiuk Franek , Wood Aaron
Published: February 2021

TouchTerrain is a simple-to-use web application that makes creating 3D printable terrain models from anywhere on the globe accessible to a wide range of users, from people with no GIS expertise to power users. For coders, a Python-based standalone version is available from the open-source project’s GitHub repository. Analyzing 18 months of web analytics gave us a preliminary look at who is using the TouchTerrain web application and what their models are used for; and to map out what terrains on the globe they chose to 3D print. From July 2019 to January 2021, more than 20,000 terrain models were downloaded. Models were created for many different use cases, including education, research, outdoor activities and crafting mementos. Most models were realized with 3D printers, but a sizable minority used CNC machines. Our own experiences with using 3D printed terrain in a university setting have been very positive so far. Anecdotal evidence points to the strong potential for 3D printed terrain models to provide significant help with specific map-related tasks. For the introductory geology laboratory, 3D printed models were used as a form of “training wheels” to aid beginning students in learning to read contour maps, which are still an important tool for geology.
Investigation of the Expression Method of Theme-Typhoon Disaster Information
Authors: Xiao Cong , Zhang Xiaodong , Xing Ziyao , Han Keke , Liu Zhe , Liu Junming
Published: February 2021

Typhoon disaster information is characterized by multiple sources, complexity and diversity, and different users of this content have different individual concerns. The expression methods of typhoon disaster information considered in previous research have been relatively simple, which cannot meet the personalized service needs of different users. In this paper, according to the diverse content needs of different users in distinct stages of a typhoon disaster, a typhoon disaster information expression method with a multi-user, multi-stage, multi-channel and multi-element combined mode is investigated. First, the audience and disaster stages are divided via demand analysis, and the demand content is summarized according to the users, stages, and release channels. Similar information is then integrated into the same theme, and it is also determined how information is expressed. Then, the analytic hierarchy process (AHP) is used to filter out the important information in each theme. The theme template is then designed according to the characteristics of particular release channels. Finally, a prototype system is developed, and Typhoon Lekima, which impacted China in 2019, is considered as a real case for analysis. The results show that the proposed method can effectively support different users to obtain disaster characteristics at distinct stages of typhoon disasters, evaluate disaster conditions, assist scientific decision-making, and enhance public awareness of risk prevention.
A Framework of Dam-Break Hazard Risk Mapping for a Data-Sparse Region in Indonesia
Authors: Yudianto Doddi , Ginting Bobby Minola , Sanjaya Stephen , Rusli Steven Reinaldo , Wicaksono Albert
Published: February 2021

This paper introduces a new simple approach for dam-break hazard mapping in a data-sparse region. A hypothetical breaching case of an earthen dam, i.e., the Ketro Dam in Central Java, (Indonesia) was considered. Open-access hydrological databases, i.e., TRMM and CHIRPS, were collected and compared with the rainfall ground station data to ensure data quality. Additionally, the 3-h rainfall distribution of the TRMM database was employed and validated with the measured data to establish the 24-h rainfall distribution of the probable maximum precipitation. The probable maximum flood discharge was computed with the SCS method, and the reservoir routing computation was conducted to determine the possible breaching mechanisms. The result shows that the Ketro Dam proves safe against overtopping, and thus only the piping mechanism has been taken into consideration. Using the breaching hydrograph, the open-access Digital Elevation Model MERIT Hydro, and the high-performance shallow water model NUFSAW2D, the flood propagation to the downstream part of the dam was simulated, enabling fast computations for different scenarios. The quantification of the susceptibility rate of urban areas was eased with overlay analysis utilizing InaSAFE, a plugin for the QGIS model. This study shows that even for a data-sparse region, the recent open-access databases in terms of hydrological and hydraulic aspects may be used to generate a dam-break hazard map. This will benefit the related stakeholders to take proper action to reduce the loss of life.
Bus Service Level and Horizontal Equity Analysis in the Context of the Modifiable Areal Unit Problem
Authors: Ruiz-Pérez Maurici , Seguí-Pons Joana Maria
Published: February 2021

The modifiable areal unit problem is of great importance in geographic science. The use of a specific zoning impacts the social and economic imbalances that can be generated in the deployment of services, facilities, and infrastructure. In this article, GIS is used together with simulation and optimization tools to analyse the effects of bus frequency changes in the levels of service and horizontal equity derived from different types of territorial zoning. The city of Palma (Balearic Islands, Spain) was chosen as a case study for the method, for which different geographical areas are used: neighbourhoods, census sections, cadastral blocks, and a 400 × 400 m mesh. The results show significant variations of the optimal frequencies obtained, depending on the type of zoning used. In general, smaller zonings show much higher sensitivity for the detection of imbalances between the population and bus service level. Likewise, orthogonal zonings also prove useful for identifying service and population concentration over other zonings. The use of large spatial units could lead to the misdiagnosis of needs and the implementation of actions that do not actually improve the level of service or the equity of the transport service. It is recommended to consider combining zonings of different sizes simultaneously, in order to accurately highlight imbalances and to argue for transport service improvements.
Trogocytosis between Non-Immune Cells for Cell Clearance, and among Immune-Related Cells for Modulating Immune Responses and Autoimmunity
Authors: Li Ko-Jen , Wu Cheng-Han , Lu Cheng-Hsun , Shen Chieh-Yu , Kuo Yu-Min , Tsai Chang-Youh , Hsieh Song-Chou , Yu Chia-Li
Published: February 2021

The term trogocytosis refers to a rapid bidirectional and active transfer of surface membrane fragment and associated proteins between cells. The trogocytosis requires cell-cell contact, and exhibits fast kinetics and the limited lifetime of the transferred molecules on the surface of the acceptor cells. The biological actions of trogocytosis include information exchange, cell clearance of unwanted tissues in embryonic development, immunoregulation, cancer surveillance/evasion, allogeneic cell survival and infectious pathogen killing or intercellular transmission. In the present review, we will extensively review all these aspects. In addition to its biological significance, aberrant trogocytosis in the immune system leading to autoimmunity and immune-mediated inflammatory diseases will also be discussed. Finally, the prospective investigations for further understanding the molecular basis of trogocytosis and its clinical applications will also be proposed.
Fatal Attraction: The Case of Toxic Soluble Dimers of Truncated PQBP-1 Mutants in X-Linked Intellectual Disability
Authors: Chen Yu Wai , Rahman Shah Kamranur
Published: February 2021

The frameshift mutants K192Sfs*7 and R153Sfs*41, of the polyglutamine tract-binding protein 1 (PQBP-1), are stable intrinsically disordered proteins (IDPs). They are each associated with the severe cognitive disorder known as the Renpenning syndrome, a form of X-linked intellectual disability (XLID). Relative to the monomeric wild-type protein, these mutants are dimeric, contain more folded contents, and have higher thermal stabilities. Comparisons can be drawn to the toxic oligomerisation in the “conformational diseases”, which collectively describe medical conditions involving a substantial protein structural transition in the pathogenic mechanism. At the molecular level, the end state of these diseases is often cytotoxic protein aggregation. The conformational disease proteins contain varying extents of intrinsic disorder, and the consensus pathogenesis includes an early oligomer formation. We reviewed the experimental characterisation of the toxic oligomers in representative cases. PQBP-1 mutant dimerisation was then compared to the oligomerisation of the conformational disease proteins. The PQBP-1 mutants are unique in behaving as stable soluble dimers, which do not further develop into higher oligomers or aggregates. The toxicity of the PQBP-1 mutant dimers lies in the native functions (in transcription regulation and possibly, RNA splicing) being compromised, rather than proceeding to aggregation. Other examples of stable IDP dimers were discussed and we speculated on the roles of IDP dimerisation in protein evolution.
New 3-Aryl-2-(2-thienyl)acrylonitriles with High Activity Against Hepatoma Cells
Authors: Schaller Eva , Ma Andi , Gosch Lisa Chiara , Klefenz Adrian , Schaller David , Goehringer Nils , Kaps Leonard , Schuppan Detlef , Volkamer Andrea , Schobert Rainer , Biersack Bernhard , Nitzsche Bianca , Höpfner Michael
Published: February 2021

New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, while no contribution of unspecific cytotoxic effects was observed in LDH-release measurements. Kinase profiling of cancer relevant protein kinases identified the two 3-aryl-2-(thien-2-yl)acrylonitrile derivatives 1b and 1c as (multi-)kinase inhibitors with a preferential activity against the VEGFR-2 tyrosine kinase. Additional bioinformatic analysis of the VEGFR-2 binding modes by docking and molecular dynamics calculations supported the experimental findings and indicated that the hydroxy group of 1c might be crucial for its distinct inhibitory potency against VEGFR-2. Forthcoming studies will further unveil the underlying mode of action of the promising new derivatives as well as their suitability as an urgently needed novel approach in HCC treatment.
The Distribution of Several Genomic Virulence Determinants Does Not Corroborate the Established Serotyping Classification of Bacillus thuringiensis
Authors: Shikov Anton E. , Malovichko Yury V. , Lobov Arseniy A. , Belousova Maria E. , Nizhnikov Anton A. , Antonets Kirill S.
Published: February 2021

Bacillus thuringiensis, commonly referred to as Bt, is an object of the lasting interest of microbiologists due to its highly effective insecticidal properties, which make Bt a prominent source of biologicals. To categorize the exuberance of Bt strains discovered, serotyping assays are utilized in which flagellin serves as a primary seroreactive molecule. Despite its convenience, this approach is not indicative of Bt strains’ phenotypes, neither it reflects actual phylogenetic relationships within the species. In this respect, comparative genomic and proteomic techniques appear more informative, but their use in Bt strain classification remains limited. In the present work, we used a bottom-up proteomic approach based on fluorescent two-dimensional difference gel electrophoresis (2D-DIGE) coupled with liquid chromatography/tandem mass spectrometry(LC-MS/MS) protein identification to assess which stage of Bt culture, vegetative or spore, would be more informative for strain characterization. To this end, the proteomic differences for the israelensis-attributed strains were assessed to compare sporulating cultures of the virulent derivative to the avirulent one as well as to the vegetative stage virulent bacteria. Using the same approach, virulent spores of the israelensis strain were also compared to the spores of strains belonging to two other major Bt serovars, namely darmstadiensis and thuringiensis. The identified proteins were analyzed regarding the presence of the respective genes in the 104 Bt genome assemblies available at open access with serovar attributions specified. Of 21 proteins identified, 15 were found to be encoded in all the present assemblies at 67% identity threshold, including several virulence factors. Notable, individual phylogenies of these core genes conferred neither the serotyping nor the flagellin-based phylogeny but corroborated the reconstruction based on phylogenomics approaches in terms of tree topology similarity. In its turn, the distribution of accessory protein genes was not confined to the existing serovars. The obtained results indicate that neither gene presence nor the core gene sequence may serve as distinctive bases for the serovar attribution, undermining the notion that the serotyping system reflects strains’ phenotypic or genetic similarity. We also provide a set of loci, which fit in with the phylogenomics data plausibly and thus may serve for draft phylogeny estimation of the novel strains.
Selective Cardiomyocyte Oxidative Stress Leads to Bystander Senescence of Cardiac Stromal Cells
Authors: Martini Hélène , Lefevre Lise , Sayir Sylvain , Itier Romain , Maggiorani Damien , Dutaur Marianne , Marsal Dimitri J. , Roncalli Jérôme , Pizzinat Nathalie , Cussac Daniel , Parini Angelo , Mialet-Perez Jeanne , Douin-Echinard Victorine
Published: February 2021

Accumulation of senescent cells in tissues during normal or accelerated aging has been shown to be detrimental and to favor the outcomes of age-related diseases such as heart failure (HF). We have previously shown that oxidative stress dependent on monoamine oxidase A (MAOA) activity in cardiomyocytes promotes mitochondrial damage, the formation of telomere-associated foci, senescence markers, and triggers systolic cardiac dysfunction in a model of transgenic mice overexpressing MAOA in cardiomyocytes (Tg MAOA). However, the impact of cardiomyocyte oxidative stress on the cardiac microenvironment in vivo is still unclear. Our results showed that systolic cardiac dysfunction in Tg MAOA mice was strongly correlated with oxidative stress induced premature senescence of cardiac stromal cells favoring the recruitment of CCR2+ monocytes and the installation of cardiac inflammation. Understanding the interplay between oxidative stress induced premature senescence and accelerated cardiac dysfunction will help to define new molecular pathways at the crossroad between cardiac dysfunction and accelerated aging, which could contribute to the increased susceptibility of the elderly to HF.
Targeting Copper Homeostasis Improves Functioning of vps13Δ Yeast Mutant Cells, a Model of VPS13-Related Diseases
Authors: Soczewka Piotr , Tribouillard-Tanvier Déborah , di Rago Jean-Paul , Zoladek Teresa , Kaminska Joanna
Published: February 2021

Ion homeostasis is crucial for organism functioning, and its alterations may cause diseases. For example, copper insufficiency and overload are associated with Menkes and Wilson’s diseases, respectively, and iron imbalance is observed in Parkinson’s and Alzheimer’s diseases. To better understand human diseases, Saccharomyces cerevisiae yeast are used as a model organism. In our studies, we used the vps13Δ yeast strain as a model of rare neurological diseases caused by mutations in VPS13A–D genes. In this work, we show that overexpression of genes encoding copper transporters, CTR1, CTR3, and CCC2, or the addition of copper salt to the medium, improved functioning of the vps13Δ mutant. We show that their mechanism of action, at least partially, depends on increasing iron content in the cells by the copper-dependent iron uptake system. Finally, we present that treatment with copper ionophores, disulfiram, elesclomol, and sodium pyrithione, also resulted in alleviation of the defects observed in vps13Δ cells. Our study points at copper and iron homeostasis as a potential therapeutic target for further investigation in higher eukaryotic models of VPS13-related diseases.
The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin
Authors: Athanasiou Evita , Gargalionis Antonios N. , Boufidou Fotini , Tsakris Athanassios
Published: February 2021

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.
Construction of Boronophenylalanine-Loaded Biodegradable Periodic Mesoporous Organosilica Nanoparticles for BNCT Cancer Therapy
Authors: Tamanoi Fuyuhiko , Chinnathambi Shanmugavel , Laird Mathilde , Komatsu Aoi , Birault Albane , Takata Takushi , Doan Tan Le-Hoang , Mai Ngoc Xuan Dat , Raitano Arthur , Morrison Kendall , Suzuki Minoru , Matsumoto Kotaro
Published: February 2021

Biodegradable periodic mesoporous organosilica (BPMO) has recently emerged as a promising type of mesoporous silica-based nanoparticle for biomedical applications. Like mesoporous silica nanoparticles (MSN), BPMO possesses a large surface area where various compounds can be attached. In this work, we attached boronophenylalanine (10BPA) to the surface and explored the potential of this nanomaterial for delivering boron-10 for use in boron neutron capture therapy (BNCT). This cancer therapy is based on the principle that the exposure of boron-10 to thermal neutron results in the release of α-particles that kill cancer cells. To attach 10BPA, the surface of BPMO was modified with diol groups which facilitated the efficient binding of 10BPA, yielding 10BPA-loaded BPMO (10BPA-BPMO). Surface modification with phosphonate was also carried out to increase the dispersibility of the nanoparticles. To investigate this nanomaterial’s potential for BNCT, we first used human cancer cells and found that 10BPA-BPMO nanoparticles were efficiently taken up into the cancer cells and were localized in perinuclear regions. We then used a chicken egg tumor model, a versatile and convenient tumor model used to characterize nanomaterials. After observing significant tumor accumulation, 10BPA-BPMO injected chicken eggs were evaluated by irradiating with neutron beams. Dramatic inhibition of the tumor growth was observed. These results suggest the potential of 10BPA-BPMO as a novel boron agent for BNCT.
New Insights Into Oral Squamous Cell Carcinoma: From Clinical Aspects to Molecular Tumorigenesis
Authors: Chen Shang-Hung , Hsiao Sheng-Yen , Chang Kwang-Yu , Chang Jang-Yang
Published: February 2021

Oral squamous cell carcinoma (SCC) is a prevalent malignant disease worldwide, especially so in Taiwan. Early- or even preclinical-stage detection is critical for reducing morbidity and mortality from oral SCC. Epidemiological and genome association studies are useful for identifying clinicopathological risk factors for preventive, diagnostic, and therapeutic approaches of oral SCC. For advanced oral SCC, effective treatments are critical to prolonging survival and enhancing quality of life. As oral SCC is characteristic of regional invasion with lymph node metastases, understanding the aggressive features of oral SCC, particularly in lymphangiogenesis, is essential for determining effective treatments. Emerging evidence has demonstrated that the tumor microenvironment (TME) plays a pivotal role in tumor growth, invasion, and metastases. Recent clinical successes in immune checkpoint inhibitors either alone or combined with chemotherapy have also supported the therapeutic value of immunotherapy in oral SCC. This review summarizes critical advances in basic knowledge of oral SCC from the perspective of clinicopathological risk factors, molecular tumorigenesis, and the TME. We also highlight our recent investigations on the microbiome, genome association studies, lymphangiogenesis, and immunomodulation in oral SCC. This review may provide new insights for oral SCC treatment by systematically interpreting emerging evidence from various preclinical and clinical studies.
Advances in Sensing, Response and Regulation Mechanism of Salt Tolerance in Rice
Authors: Ponce Kimberly S. , Guo Longbiao , Leng Yujia , Meng Lijun , Ye Guoyou
Published: February 2021

Soil salinity is a serious menace in rice production threatening global food security. Rice responses to salt stress involve a series of biological processes, including antioxidation, osmoregulation or osmoprotection, and ion homeostasis, which are regulated by different genes. Understanding these adaptive mechanisms and the key genes involved are crucial in developing highly salt-tolerant cultivars. In this review, we discuss the molecular mechanisms of salt tolerance in rice—from sensing to transcriptional regulation of key genes—based on the current knowledge. Furthermore, we highlight the functionally validated salt-responsive genes in rice.
Cyanidin 3-O-galactoside: A Natural Compound with Multiple Health Benefits
Authors: Liang Zhongxin , Liang Hongrui , Guo Yizhan , Yang Dong
Published: February 2021

Cyanidin 3-O-galactoside (Cy3Gal) is one of the most widespread anthocyanins that positively impacts the health of animals and humans. Since it is available from a wide range of natural sources, such as fruits (apples and berries in particular), substantial studies were performed to investigate its biosynthesis, chemical stability, natural occurrences and content, extraction methods, physiological functions, as well as potential applications. In this review, we focus on presenting the previous studies on the abovementioned aspects of Cy3Gal. As a conclusion, Cy3Gal shares a common biosynthesis pathway and analogous stability with other anthocyanins. Galactosyltransferase utilizing uridine diphosphate galactose (UDP-galactose) and cyanidin as substrates is unique for Cy3Gal biosynthesis. Extraction employing different methods reveals chokeberry as the most practical natural source for mass-production of this compound. The antioxidant properties and other health effects, including anti-inflammatory, anticancer, antidiabetic, anti-toxicity, cardiovascular, and nervous protective capacities, are highlighted in purified Cy3Gal and in its combination with other polyphenols. These unique properties of Cy3Gal are discussed and compared with other anthocyanins with related structure for an in-depth evaluation of its potential value as food additives or health supplement. Emphasis is laid on the description of its physiological functions confirmed via various approaches.
New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform
Authors: Abad-Morales Víctor , Wert Ana , Ruiz Gómez María Ángeles , Navarro Rafael , Pomares Esther
Published: February 2021

This study aims to genetically characterize a two-year-old patient suffering from multiple systemic abnormalities, including skeletal, nervous and developmental involvements and Leber congenital amaurosis (LCA). Genetic screening by next-generation sequencing identified two heterozygous pathogenic variants in nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) as the molecular cause of the disease: c.439+5G>T and c.299+526_*968dup.This splice variant has never been reported to date, whereas pathogenic duplication has recently been associated with cases displaying an autosomal recessive disorder that includes a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability and LCA (SHILCA), as well as some brain anomalies. Our patient presented clinical manifestations which correlated strongly with this reported syndrome. To further study the possible transcriptional alterations resulting from these mutations, mRNA expression assays were performed in the patient and her father. The obtained results detected aberrant alternative transcripts and unbalanced levels of expression, consistent with severe systemic involvement. Moreover, these analyses also detected a novel NMNAT1 isoform, which is variably expressed in healthy human tissues. Altogether, these findings represent new evidence of the correlation of NMNAT1 and SHILCA syndrome, and provide additional insights into the healthy and pathogenic expression of this gene.
Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology
Authors: Verma Avnish , Orme Merve Ayse , Remeškevičius Vytautas , Sobiecka Pola , Taylor Luke , Lawton Scott , Jones Ben P , Polycarpou Elena , Bennett Jason , Rooney Brian
Published: February 2021

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.