bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant-Based Phytochemicals as Possible Alternative to Antibiotics in Combating Bacterial Drug Resistance
Authors: AlSheikh Hana Mohammed Al , Sultan Insha , Kumar Vijay , Rather Irfan A. , Al-Sheikh Hashem , Tasleem Jan Arif , Haq Qazi Mohd Rizwanul
Published: August 2020

The unprecedented use of antibiotics that led to development of resistance affect human health worldwide. Prescription of antibiotics imprudently and irrationally in different diseases progressed with the acquisition and as such development of antibiotic resistant microbes that led to the resurgence of pathogenic strains harboring enhanced armors against existing therapeutics. Compromised the treatment regime of a broad range of antibiotics, rise in resistance has threatened human health and increased the treatment cost of diseases. Diverse on metabolic, genetic and physiological fronts, rapid progression of resistant microbes and the lack of a strategic management plan have led researchers to consider plant-derived substances (PDS) as alternative or in complementing antibiotics against the diseases. Considering the quantitative characteristics of plant constituents that attribute health beneficial effects, analytical procedures for their isolation, characterization and phytochemical testing for elucidating ethnopharmacological effects has being worked out for employment in the treatment of different diseases. With an immense potential to combat bacterial infections, PDSs such as polyphenols, alkaloids and tannins, present a great potential for use, either as antimicrobials or as antibiotic resistance modifiers. The present study focuses on the mechanisms by which PDSs help overcome the surge in resistance, approaches for screening different phytochemicals, methods employed in the identification of bioactive components and their testing and strategies that could be adopted for counteracting the lethal consequences of multidrug resistance.
An Off-Line DPPH-GC-MS Coupling Countercurrent Chromatography Method for Screening, Identification, and Separation of Antioxidant Compounds in Essential Oil
Authors: Wang Xiang , Zuo Guang-Lei , Wang Chao-Yue , Kim Hyun Yong , Lim Soon Sung , Tong Sheng-Qiang
Published: August 2020

Essential oils are an important source of natural antioxidants and multiple methods have been established for evaluation of their overall antioxidant activity, however, the antioxidant activities of their compounds are less investigated. In the present study, the hyphenation of 2,2′-diphenyl-1-picrylhydrazyl (DPPH)-gas chromatography (GC)-mass spectrometry (MS) offline and high-speed countercurrent chromatography (HSCCC) is established for efficient screening, identification, and isolation of antioxidants from essential oils and applied to the essential oil of Curcuma wenyujin Y.H. Chen et C. Ling. Five compounds are preliminarily screened as antioxidants using DPPH-GC according to the reduction of GC peak areas of each compound after reaction with DPPH and then identified as eucalyptol (7.66%), camphor (2.34%), δ-elemene (1.15%), β-elemene (7.10%), and curzerene (15.77%) using GC-MS. Moreover, these five compounds are isolated by HSCCC using two solvent systems, n-hexane-acetonitrile-ethanol (5:3:2, v/v) and n-hexane-acetonitrile-acetone (4:3:1, v/v), and subjected to DPPH scavenging assay. Camphor, δ-elemene, and β-elemene show weak DPPH scavenging activity, while curzerene and eucalyptol show moderate DPPH scavenging activity. Notably, a significant synergistic effect on DPPH scavenging is found between curzerene and eucalyptol. The result demonstrated that off-line DPPH-GC-MS coupling CCC is an efficient method for screening, identification, and separation of antioxidant compounds in essential oil
Enzymatic Antioxidant Signatures in Hyperthermophilic Archaea
Authors: Pedone Emilia , Fiorentino Gabriella , Bartolucci Simonetta , Limauro Danila
Published: August 2020

To fight reactive oxygen species (ROS) produced by both the metabolism and strongly oxidative habitats, hyperthermophilic archaea are equipped with an array of antioxidant enzymes whose role is to protect the biological macromolecules from oxidative damage. The most common ROS, such as superoxide radical (O2•−) and hydrogen peroxide (H2O2), are scavenged by superoxide dismutase, peroxiredoxins, and catalase. These enzymes, together with thioredoxin, protein disulfide oxidoreductase, and thioredoxin reductase, which are involved in redox homeostasis, represent the core of the antioxidant system. In this review, we offer a panorama of progression of knowledge on the antioxidative system in aerobic or microaerobic (hyper)thermophilic archaea and possible industrial applications of these enzymes.
Antioxidants and Skin Protection
Authors: Herranz-López María , Barrajón-Catalán Enrique
Published: August 2020

Natural products have a long history of use for skincare and the improvement of the appearance and function of aged and/or damaged skin [...]
Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy
Authors: Martins Beatriz , Amorim Madania , Reis Flávio , Ambrósio António Francisco , Fernandes Rosa
Published: August 2020

Diabetic retinopathy (DR) is a complex, progressive, and heterogenous retinal degenerative disease associated with diabetes duration. It is characterized by glial, neural, and microvascular dysfunction, being the blood-retinal barrier (BRB) breakdown a hallmark of the early stages. In advanced stages, there is formation of new blood vessels, which are fragile and prone to leaking. This disease, if left untreated, may result in severe vision loss and eventually legal blindness. Although there are some available treatment options for DR, most of them are targeted to the advanced stages of the disease, have some adverse effects, and many patients do not adequately respond to the treatment, which demands further research. Oxidative stress and low-grade inflammation are closely associated processes that play a critical role in the development of DR. Retinal cells communicate with each other or with another one, using cell junctions, adhesion contacts, and secreted soluble factors that can act in neighboring or long-distance cells. Another mechanism of cell communication is via secreted extracellular vesicles (EVs), through exchange of material. Here, we review the current knowledge on deregulation of cell-to-cell communication through EVs, discussing the changes in miRNA expression profiling in body fluids and their role in the development of DR. Thereafter, current and promising therapeutic agents for preventing the progression of DR will be discussed.
End-Users’ Augmented Reality Utilization for Architectural Design Review
Authors: Lee Jin Gang , Seo JoonOh , Abbas Ali , Choi Minji
Published: August 2020

To effectively use augmented reality (AR) technology for end-user involved design collaboration, it is necessary to ensure the effectiveness of the AR system from the end-user’s perspective. However, most efforts have mainly focused on technological development, and as such, limited attention has been paid to the end-user’s application of the AR system. Therefore, this study investigates how the AR system affects architectural design review based on the user’s perspectives. Three different display systems presenting a 3D model including a 2D screen, VR, and AR were tested, and a total of 76 participants evaluated visual presentation quality, perceived acceptability, and user experience according to their usage of the visualization platform types during the design review activities. Compared to other systems, the results indicated that the AR system could be more effective in reviewing the visual elements of a building. Furthermore, AR showed the highest ratings for acceptance level and user experience. The innovation provided by AR created a positive user experience, despite its remaining challenges to be resolved in terms of functionality. Since it is expected that the use of AR can be promoted by overcoming certain technological limitations, this study contributes to guiding AR system applications for end-users involved in the design review process.
Spectroscopic Characterization of Iron Slags from the Archaeological Sites of Brâncoveneşti, Călugăreni and Vătava Located on the Mureş County (Romania) Sector of the Roman Limes
Authors: Bitay Enikő , Kacsó Irina , Tănăselia Claudiu , Toloman Dana , Borodi Gheorghe , Pánczél Szilamér-Péter , Kisfaludi-Bak Zsombor , Veress Erzsébet
Published: August 2020

Iron slag samples unearthed from archaeological sites lying on the Eastern limes sector of Roman Dacia (the Brâncoveneşti and Călugăreni auxiliary forts and the Vătava watchtower) were studied in order to assess the probability of local iron working (smelting and smithing) during the 2nd–3rd centuries CE. Structural-mineralogic aspects revealed by PXRD analysis and FTIR spectroscopy indicate different slag types corresponding to different iron production and processing stages allowing the supposition that refining of the bloom and processing of the refined iron took place on the sites. The FTIR absorption bands obtained in the spectral domain 2000–400 cm−1 show that mineralogically the samples are constituted mainly of silicates associated with minor quantities of aluminates and carbonates. The fayalite, haematite, and magnetite phases appearing on both the X-ray diffractograms and the FTIR spectra agree with the redox conditions of the slag formation process which result from the Fe3+/Fe2+ ratio determined using the EPR-method. The bulk macro-elemental PXRF and ICP-MS spectroscopy data support the slag typization proposed on the basis of the probable working conditions; trace-elemental bulk composition suggests that the provenance of the raw materials may be different.
Research on Lifespan Prediction of Cross-Linked Polyethylene Material for XLPE Cables
Authors: Zhang Yi , Wu Zaijun , Qian Cheng , Tan Xiao , Yang Jinggang , Zhong Linlin
Published: August 2020

In this paper, cross-linked polyethylene (XLPE) cables of the same batch from Factory A, which ran from 1 to 8 years in Jiangsu Province, are sampled. Some widely accepted aging characterization methods of XLPE cables such as the gel content test, differential scanning calorimetry (DSC) test, tensile test and hardness test are employed to obtain the physicochemical, mechanical and electrical properties of the samples. Then, some lifespan prediction parameters significantly correlated with operating time are obtained through correlation calculations. Finally, a prediction method is proposed to predict the operating time of XLPE cables from Factory A. The test results indicate that parameters including the gel content Cge, the crystallinity XC, tensile strength σ, ultimate elongation δ, the dielectric permittivity ε, and the dielectric loss Jtan are significantly correlated with operating time, which can be used in evaluating the aging degree of XLPE cables. Moreover, due to the high accuracy of the experimental verification, it turns out that the lifespan prediction method proposed in this paper can be used to determine the operating time of XLPE cables from Factory A in future research.
Leguminous Seeds Powder Diet Reduces the Survival and Development of the Khapra beetle, Trogoderma granarium Everts (Coleoptera: Dermestidae)
Authors: Mantzoukas Spiridon , Korbou Georgia , Magita Alexandra , A. Eliopoulos Panagiotis , Poulas Konstantinos
Published: August 2020

Chemical storage pest control is interlinked with many challenges such as environmental pollution and toxicity to humans and animals. Alternative tools are thus being increasingly researched and applied to supplement and/or substitute old-fashioned chemical means. Entomotoxic proteins, such as the lectins of leguminous seeds, have been shown to be effective alternative control agents against many serious insect pests. The objective of this work was to evaluate the effect of the flour of three leguminous seeds, Phaseolus vulgaris L. (Fabaceae) (the common bean), Vicia faba L. (Fabaceae) (the broad bean) and Glycine max L. (Fabaceae) (the soya bean), against 4th instar larvae of Trogoderma granarium Everts (Coleoptera: Curculionidae). The flours were tested at different concentrations. They all demonstrated significant effects on larval mortality, as well as they all induced a decrease in the number of larvae reaching the pupal stage. The flours of P. vulgaris and V. faba were highly insecticidal against T. granarium larvae, especially at the highest concentrations (86.7% for PV100 and 90% for VF100). Our results enrich previous findings on the entomotoxic effect of leguminous plant lectins and highlight P. vulgaris and V. faba lectins as potential alternative control agents against T. granarium.
Distinct Calcium Binding and Structural Properties of Two Centrin Isoforms from Toxoplasma gondii
Authors: Bombardi Luca , Pedretti Marco , Conter Carolina , Dominici Paola , Astegno Alessandra
Published: August 2020

Centrins are calcium (Ca2+)-binding proteins that have been implicated in several regulatory functions. In the protozoan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, three isoforms of centrin have been identified. While increasing information is now available that links the function of centrins with defined parasite biological processes, knowledge is still limited on the metal-binding and structural properties of these proteins. Herein, using biophysical and structural approaches, we explored the Ca2+ binding abilities and the subsequent effects of Ca2+ on the structure of a conserved (TgCEN1) and a more divergent (TgCEN2) centrin isoform from T. gondii. Our data showed that TgCEN1 and TgCEN2 possess diverse molecular features, suggesting that they play nonredundant roles in parasite physiology. TgCEN1 binds two Ca2+ ions with high/medium affinity, while TgCEN2 binds one Ca2+ with low affinity. TgCEN1 undergoes significant Ca2+-dependent conformational changes that expose hydrophobic patches, supporting a role as a Ca2+ sensor in toxoplasma. In contrast, Ca2+ binding has a subtle influence on conformational features of TgCEN2 without resulting in hydrophobic exposure, suggesting a different Ca2+ relay mode for this isoform. Furthermore, TgCEN1 displays a Ca2+-dependent ability to self-assemble, while TgCEN2 did not. We discuss our findings in the context of Ca2+ signaling in toxoplasma.
Identification of Cardiac Glycosides as Novel Inhibitors of eIF4A1-Mediated Translation in Triple-Negative Breast Cancer Cells
Authors: Howard Cory M. , Estrada Matthew , Terrero David , Tiwari Amit K. , Raman Dayanidhi
Published: August 2020

The eukaryotic translation initiation factor 4F complex (eIF4F) is a potential chemotherapeutic target in triple-negative breast cancer (TNBC). This complex regulates cap-dependent translational initiation and consists of three core proteins: eIF4E, eIF4G, and eIF4A1. In this study, we focus on repositioning compounds as novel inhibitors of eIF4A1-mediated translation. In order to accomplish this goal, a modified synthetic reporter assay was established. More specifically, a (CGG)4 motif, which confers eIF4A dependency, was incorporated into the 5’-leader region of a luciferase-tdTomato lentiviral reporter construct. The Prestwick Chemical Library was then screened in multiple TNBC cell lines by measuring the tdTomato fluorescent intensity. We identified several cardiac glycosides as potential inhibitors of eIF4A1-mediated translation. Based on our studies, we find that cardiac glycosides inhibit the expression of eIF4A1. To identify a potential mechanism by which this was occurring, we utilized the Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our pursuits led us to the discovery that cardiac glycosides also decrease levels of c-MYC. Quantitative PCR confirmed that decreases in c-MYC and eIF4A were occurring at the transcriptional level. As such, disruption of the eIF4A1-c-MYC axis may be a viable approach in the treatment of TNBC. The novel combination of rocaglamide A and digoxin exhibited synergistic anti-cancer activity against TNBC cells in vitro. The findings in this study and others are important for formulating potential combination chemotherapies against eIF4A1 in vivo. Thus, drug repositioning may be one classical approach to successfully target eIF4A1 in TNBC patients.
Active Learning Augmented Reality for STEAM Education—A Case Study
Authors: Jesionkowska Joanna , Wild Fridolin , Deval Yann
Published: August 2020

Immersive technologies are rapidly transforming the field of education. Amongst them, Augmented Reality (AR) has shown promise as a resource, particularly for education in Science, Technology, Engineering, Arts, and Mathematics (STEAM). There are, however, few teachers deploying this new medium in the classroom directly, and, consequently, only a few, elect students benefit from the AR-enriched offers. Curricula are already overloaded, and schools generally lack developmental resources, thus leaving no room for experimentation. This situation is further aggravated by the too few educational applications available with sufficient learning content. In this article, we investigate the method of Active Learning for the teaching of STEAM subjects, using a format where students are tasked with building an AR application as part of their learning. We evaluate the applicability of the Active Learning for STEAM subjects with a qualitative, case study approach, applying the workshop format as an extracurricular activity in our work with students from a range of secondary schools in Oxford. We discuss how the format works, so it can be embedded into regular curricula, not just as an extracurricular activity, also providing an overview on the involved teaching units and rationale. All teams in our preview audience of the case study succeeded in building working applications, several of impressive complexity. Students found that the lessons were enjoyable and AR technology can enhance their learning experience. The Active Learning method served as a catalyst for students’ skills development, with the case study providing evidence of learning to code, working with a physics simulation engine, ray-tracing, and geometry, learning how to manage teams and interact with other students/instructors, and engineering a working prototype of a game. We consequentially argue that combining the STEM subjects and the arts, using the proposed Active Learning format, is able to provide a more holistic and engaging education.
Improved Road Segment-Based Geographical Routing Protocol for Vehicular Ad-hoc Networks
Authors: Qureshi Kashif Naseer , Islam Farooq Ul , Kaiwartya Omprakash , Kumar Arvind , Lloret Jaime
Published: August 2020

The real-time traffic information dissemination among on-road vehicles has been envisioned via realizing vehicular ad hoc networks (VANETs) as smart service-oriented roadside wireless sensor networks. The network enables various types of real-time traffic applications related to safety and infotainment for drivers and passengers. The information dissemination-centric routing protocols for vehicular networks have to dynamically adopt under the constrained network environment while considering the higher mobility of vehicular nodes and unpredictable physical topologies in the network. The issue needs to be addressed through smart and network-aware routing protocols. Geographical routing protocols have witnessed significant attention for information dissemination under these types of dynamic vehicular network environment. To this end, this paper presents an improved road segment-based geographical routing (ISR) protocol focusing on better head node selection for information dissemination. It divides the forwarding area into a number of road segments and selects a head node on each segment by focusing on traffic-aware information including the location, direction, and link quality-centric score for every vehicle on each road segment. Algorithms were developed for the complete process of head node selection and information dissemination among vehicles on the road segments. The simulation results attested the performance benefits of the proposed routing framework as compared to the state-of-the-art protocols considering dynamic vehicular traffic environment-related metrics.
Characterisation of Indoor Massive MIMO Channels Using Ray-Tracing: A Case Study in the 3.2–4.0 GHz 5G Band
Authors: Valle Luis , Pérez Jesús R. , Torres Rafael P.
Published: August 2020

In this paper, research results on the applicability of ray-tracing (RT) techniques to model massive MIMO (MaMi) channels are presented and discussed. The main goal is to show the possibilities that site-specific models based on rigorous RT techniques, along with measurement campaigns considered for verification or calibration purposes where appropriate, can contribute to the development and deployment of 5G systems and beyond using the MaMi technique. For this purpose, starting from the measurements and verification of the simulator in a symmetric, rectangular and accessible scenario used as the testbed, the analysis of a specific case involving channel characterisation in a large, difficult access and measurement scenario was carried out using the simulation tool. Both the measurement system and the simulations emulated the up-link in an indoor cell in the framework of a MaMi-TDD-OFDM system, considering that the base station was equipped with an array consisting of 10 × 10 antennas. The comparison of the simulations with the measurements in the testbed environment allowed us to affirm that the accuracy of the simulator was high, both for determining the parameters of temporal dispersion and frequency selectivity, and for assessing the expected capacity in a specific environment. The subsequent analysis of the target environment showed the high capacities that a MaMi system can achieve in indoor picocells with a relatively high number of simultaneously active users.
A Hybrid System Model-Based Open-Circuit Fault Diagnosis Method of Three-Phase Voltage-Source Inverters for PMSM Drive Systems
Authors: Chen Tao , Pan Yuedou , Xiong Zhanbo
Published: August 2020

This paper presents an open-circuit (OC) fault diagnosis method of three-phase voltage-source inverters (VSIs) for permanent magnet synchronous motor (PMSM) drive systems based on the hybrid system model (HSM). On the basis of phase voltage analysis, the HSM of the PMSM-inverter system was established, which can describe the system more accurately. To quickly diagnose whether the fault occurs, a current estimator was constructed based on the healthy HSM. Different fault types of the VSI can be simulated synchronously by the HSM, and the similarity between each simulated fault type and the actual one is evaluated based on the Euclidean distance method. Therefore, the fault isolation can be carried out according to the characteristics of Euclidean distances. The proposed method has the advantages of fast diagnosis speed and strong robustness, and it does not require additional sensors. By the presented diagnosis algorithm, the fault can be detected and isolated within a time interval about 5% and 10% of the current fundamental wave period, respectively. The simulation and experimental results verify the effectiveness of the proposed method.
Development of an Elevation–Fresnel Linked Mini-Heliostat Array
Authors: Moreno-Cruz Isaías , Castro Juan Carlos , Álvarez-Brito Omar , Mota-Nava Hilda B. , Ramírez-Zúñiga Guillermo , Quiñones-Aguilar José J. , Arancibia-Bulnes Camilo A.
Published: August 2020

Heliostats are critical components of solar tower technology and different strategies have been proposed to reduce their costs; among them diminishing their size to reduce wind loads or linking nearby heliostats mechanically, to reduce the overall number of actuators. This document aims to describe the development of a linked array of mini-heliostats which move together in an elevation–Fresnel configuration. This configuration consists of an array of mirrors rotating around linked parallel axes, in a linear Fresnel style with an added elevation mechanism allowing all axes to incline simultaneously in the plane North–South–Zenith; that is equivalent to an array of N linked mini-heliostats moved by only two drives instead of 2N. A detailed analytical study of the Sun-tracking performance of this kind of heliostat arrays was carried out, and an 8-mirror prototype based on optical and mechanical analyses was designed, built and tested. Even though the mirrors are flat, the array produced a rather compact radiative flux distribution on the receiver. The flux distribution is compatible with a slope error of the order of 1 mrad. Peak and mean concentration ratios reached 6.89 and 3.94, respectively.
Education for Sustainable Energy: Comparison of Different Types of E-Learning Activities
Authors: Martín-Lara María , Rico Nuria
Published: August 2020

This paper reports a comparison of results obtained by using different e-learning strategies for teaching a biogas topic in two courses of the chemical engineering degree at the University of Granada. Particularly, four different asynchronous e-learning activities were carefully chosen: (1) noninteractive videos and audio files; (2) reading papers and discussion; (3) virtual tour of recommended websites of entities/associations/organizations working in the biogas sector; (4) PowerPoint slides and class notes. Students evaluated their satisfaction level (assessment) and teachers gave scores for evaluation exams (scores). We discuss the results from a quantitative point of view to suggest recommendations for improving e-learning implementations in education for sustainable energy. For dependent variables, reached scores and satisfaction assessment, we find the differences between means for students in two different academic years are no significant. In addition, there are no significant differences between means depending on the type of course. Significant differences appear for scores and satisfaction assessment between different activities. Finally, we deeply analyze the relationship between score and satisfaction assessment. The results show a positive correlation between assessment of e-learning activities and the score level reached by students.
How Does the Electricity Demand Profile Impact the Attractiveness of PV-Coupled Battery Systems Combining Applications?
Authors: Pena-Bello Alejandro , Barbour Edward , Gonzalez Marta C. , Yilmaz Selin , Patel Martin K. , Parra David
Published: August 2020

Energy storage is a key solution to supply renewable electricity on demand and in particular batteries are becoming attractive for consumers who install PV panels. In order to minimize their electricity bill and keep the grid stable, batteries can combine applications. The daily match between PV supply and the electricity load profile is often considered as a determinant for the attractiveness of residential PV-coupled battery systems, however, the previous literature has so far mainly focused on the annual energy balance. In this paper, we analyze the techno-economic impact of adding a battery system to a new PV system that would otherwise be installed on its own, for different residential electricity load profiles in Geneva (Switzerland) and Austin (U.S.) using lithium-ion batteries performing various consumer applications, namely PV self-consumption, demand load-shifting, avoidance of PV curtailment, and demand peak shaving, individually and jointly. We employ clustering of the household’s load profile (with 15-minute resolution) for households with low, medium, and high annual electricity consumption in the two locations using a 1:1:1 sizing ratio. Our results show that with this simple sizing rule-of-thumb, the shape of the load profile has a small impact on the net present value of batteries. Overall, our analysis suggests that the effect of the load profile is small and differs across locations, whereas the combination of applications significantly increases profitability while marginally decreasing the share of self-consumption. Moreover, without the combination of applications, batteries are far from being economically viable.
Mutation Spectrum and De Novo Mutation Analysis in Stickler Syndrome Patients with High Myopia or Retinal Detachment
Authors: Huang Li , Chen Chonglin , Wang Zhirong , Sun Limei , Li Songshan , Zhang Ting , Luo Xiaoling , Ding Xiaoyan
Published: August 2020

Stickler syndrome is a connective tissue disorder that affects multiple systems, including the visual system. Seven genes were reported to cause Stickler syndrome in patients with different phenotypes. In this study, we aimed to evaluate the mutation features of the phenotypes of high myopia and retinal detachment. Forty-two probands diagnosed with Stickler syndrome were included. Comprehensive ocular examinations were performed. A targeted gene panel test or whole exome sequencing was used to detect the mutations, and Sanger sequencing was conducted for verification and segregation analysis. Among the 42 probands, 32 (76%) presented with high myopia and 29 (69%), with retinal detachment. Pathogenic mutations were detected in 35 (83%) probands: 27 (64%) probands had COL2A1 mutations, and eight (19%) probands had COL11A1 mutations. Truncational mutations in COL2A1 were present in 21 (78%) probands. Missense mutations in COL2A1 were present in six probands, five of which presented with retinal detachment. De novo COL2A1 mutations were detected in 10 (37%) probands, with a mean paternal childbearing age of 29.64 ± 4.97 years old. The mutation features of probands with high myopia or retinal detachment showed that the probands had a high prevalence of COL2A1 mutations, truncational mutations, and de novo mutations.
Structural Insights into TOR Signaling
Authors: Tafur Lucas , Kefauver Jennifer , Loewith Robbie
Published: August 2020

The Target of Rapamycin (TOR) is a highly conserved serine/threonine protein kinase that performs essential roles in the control of cellular growth and metabolism. TOR acts in two distinct multiprotein complexes, TORC1 and TORC2 (mTORC1 and mTORC2 in humans), which maintain different aspects of cellular homeostasis and orchestrate the cellular responses to diverse environmental challenges. Interest in understanding TOR signaling is further motivated by observations that link aberrant TOR signaling to a variety of diseases, ranging from epilepsy to cancer. In the last few years, driven in large part by recent advances in cryo-electron microscopy, there has been an explosion of available structures of (m)TORC1 and its regulators, as well as several (m)TORC2 structures, derived from both yeast and mammals. In this review, we highlight and summarize the main findings from these reports and discuss both the fascinating and unexpected molecular biology revealed and how this knowledge will potentially contribute to new therapeutic strategies to manipulate signaling through these clinically relevant pathways.
Genetic Analysis Using a Multi-Parent Wheat Population Identifies Novel Sources of Septoria Tritici Blotch Resistance
Authors: Riaz Adnan , KockAppelgren Petra , Hehir James Gerard , Kang Jie , Meade Fergus , Cockram James , Milbourne Dan , Spink John , Mullins Ewen , Byrne Stephen
Published: August 2020

Zymoseptoria tritici is the causative fungal pathogen of septoria tritici blotch (STB) disease of wheat (Triticum aestivum L.) that continuously threatens wheat crops in Ireland and throughout Europe. Under favorable conditions, STB can cause up to 50% yield losses if left untreated. STB is commonly controlled with fungicides; however, a combination of Z. tritici populations developing fungicide resistance and increased restrictions on fungicide use in the EU has led to farmers relying on fewer active substances. Consequently, this serves to drive the emergence of Z. tritici resistance against the remaining chemistries. In response, the use of resistant wheat varieties provides a more sustainable disease management strategy. However, the number of varieties offering an adequate level of resistance against STB is limited. Therefore, new sources of resistance or improved stacking of existing resistance loci are needed to develop varieties with superior agronomic performance. Here, we identified quantitative trait loci (QTL) for STB resistance in the eight-founder “NIAB Elite MAGIC” winter wheat population. The population was screened for STB response in the field under natural infection for three seasons from 2016 to 2018. Twenty-five QTL associated with STB resistance were identified in total. QTL either co-located with previously reported QTL or represent new loci underpinning STB resistance. The genomic regions identified and the linked genetic markers serve as useful resources for STB resistance breeding, supporting rapid selection of favorable alleles for the breeding of new wheat cultivars with improved STB resistance.
Blue Sublime and the Time of Capital
Authors: Menozzi Filippo
Published: August 2020

This essay proposes a concept of the “blue sublime” in order to address how the contradictions of capitalist accumulation regimes manifest themselves in the hydrosphere. My argument starts from the fact that capitalism entails a shift in the imagination of the sea: from the point of view of commodity production and consumption, the sea has turned into field of extraction, resource to be exploited or waste disposal site. But capitalism also involves circulation, which casts the sea into a space of contradictions. On the one hand, the oceanic expanse can be an image for the flow of capital and commodities, and a privileged route that has been central to the mercantile expansion of the world economy. On the other hand, however, the sea can become the emblem of the limit to accumulation, and the ultimate barrier to capital’s self-expansion. The blue sublime, hence, provides an image for picturing the totality of capitalism, while in its materiality it embodies capitalism’s contingency and perishability. From this point of view, the blue sublime registers a process described by Marx as the “annihilation of space by time” proper to the universalizing tendency of capital. Through a reading of Marx’s Grundrisse, the blue sublime hence provides a tangible representation of the asymptotic tendency of capital to reach a zero time of circulation and a privileged location to grasp the material contradictions of a global modernity.
Integrating Greenhouse Cherry Tomato Production with Biofloc Tilapia Production
Authors: Pickens Jeremy M. , Danaher Jason J. , Sibley Jeff L. , Chappell Jesse A. , Hanson Terry R.
Published: August 2020

Integration of intensive aquaculture systems with greenhouse plant production has been shown to improve aquaculture water quality conditions and improve plant nutrient use efficiency. The majority of the focus of integrated systems has involved raft culture or true hydroponics. Little work has been done on soilless culture utilizing drip irrigation. This study investigates the feasibility of integrating biofloc Nile tilapia (Oreochromis niloticus) production with greenhouse cherry tomato production (Solanum lycopersicum var. cerasiforme). Nile tilapia (157 g/fish) were stocked at 40 fish/m3 and grown for 149 days. The cherry tomato cvs. “Favorita” and “Goldita” were grown with aquaculture effluent (AE) waste and compared to plants grown with conventional fertilizer (CF) in soilless culture. Plants were grown for 157 days. Few differences in yield occurred between treatments until fish harvest (117 DAT). Post fish harvest, there was an 18.4% difference in total yield between CF and AE at crop termination for “Favorita”. Differences in yield between AE and CF were observed for “Goldita” at fish harvest (117 DAT) and crop termination (157 DAT). Results from this study suggest the potential for successful integration of cherry tomato grown in a substrate-based system with AE from a tilapia biofloc production system.
Objective Analysis of Movement in Subjects with ADHD. Multidisciplinary Control Tool for Students in the Classroom
Authors: Sempere-Tortosa Mireia , Fernández-Carrasco Francisco , Mora-Lizán Francisco , Rizo-Maestre Carlos
Published: August 2020

The term Attention Deficit Hyperactivity Disorder (ADHD) has a long history of problems behind it. The origin of all these problems lies in the lack of agreement in the assessment procedures and evaluation instruments. The diagnosis is clinical and is determined by the observation and information provided by parents and teachers. So, this is highly subjective and leads to disparate results. Therefore, on the one hand the inaccuracy of the diagnosis of ADHD, which has been based on subjective criteria, together with the fact that hyperactivity is one of the main symptoms of this disorder, implies that several studies (with limitations) have been carried out to record objective measures of movement in subjects in at least the last ten years. In order to solve some of this derived problems and limitations of previous studies, a computer program has been developed to objectively record the amount of movement of subjects. The main objective of this study is threefold: first to register the amount of movement of both experimental group and control group, then to compare them with the movement registered by observers and finally to determine the validity of the software developed as a tool to support the diagnosis of ADHD. Results show that there are significant differences in the amount of objective movement between a clinical group of subjects with ADHD and a control group, obtaining a higher average of movement the experimental group. In addition, results also demonstrate that the developed software is a valid tool for the evaluation of movement that solves the limitations of previous studies. The proposed tool is developed from different aspects to give it a multidisciplinary character.
COVID-19: The Immune Responses and Clinical Therapy Candidates
Authors: Zhand Sareh , Saghaeian Jazi Marie , Mohammadi Saeed , Tarighati Rasekhi Roozbeh , Rostamian Ghassem , Kalani Mohammad Reza , Rostamian Aida , George Jacob , Douglas Mark W
Published: August 2020

The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2’s molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.
Gga-miR-3525 Targets PDLIM3 through the MAPK Signaling Pathway to Regulate the Proliferation and Differentiation of Skeletal Muscle Satellite Cells
Authors: Yin Huadong , Zhao Jing , He Haorong , Chen Yuqi , Wang Yan , Li Diyan , Zhu Qing
Published: August 2020

MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that post-transcriptionally regulate expression of their target genes. Emerging evidence demonstrates that miRNAs are important regulators in the development of skeletal muscle satellite cells (SMSCs). Our previous research showed that gga-miR-3525 is differentially expressed in breast muscle of broilers (high growth rate) and layers (low growth rate). In this study, we report a new role for gga-miR-3525 as a myogenic miRNA that regulates skeletal muscle development in chickens. Exogenous increases in the expression of gga-miR-3525 significantly inhibited proliferation and differentiation of SMSCs, whereas the opposite effects were observed in gga-miR-3525 knockdown SMSCs. We confirmed that PDLIM3 (PDZ and LIM domain 3) is a target gene of gga-miR-3525 that can promote proliferation and differentiation of SMSCs. We found that PDLIM3 overexpression elevated the abundance of phosphorylated (p-)p38 protein but that the gga-miR-3525 mimic and p38-MAPK inhibitor (SB203580) weakened the activation of p-p38. Furthermore, treatment with SB203580 reduced the promoting effect of PDLIM3 on SMSC proliferation and differentiation. Overall, our results indicate that gga-miR-3525 regulates the proliferation and differentiation of SMSCs by targeting PDLIM3 via the p38/MAPK signaling pathway in chickens.
Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer
Authors: Anand Shashi , Khan Mohammad Aslam , Khushman Moh’d , Dasgupta Santanu , Singh Seema , Singh Ajay Pratap
Published: August 2020

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association of RAB genes in pancreatic ductal adenocarcinoma (PDAC). Of the 62 RAB genes analyzed, five (RAB3A, RAB26, RAB25, RAB21, and RAB22A) exhibited statistically significant upregulation, while five (RAB6B, RAB8B, RABL2A, RABL2B, and RAB32) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported for RAB3A, RAB25, and RAB26. However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression of RAB21 compared to daily or weekly drinkers, whereas RAB25 expression was significantly higher in social drinkers, compared to occasional ones. The expression of RABL2A was significantly reduced in PDAC from diabetic patients, whereas RAB26 was significantly lower in pancreatitis patients. More importantly, a significant association of high expression of RAB21, RAB22A, and RAB25, and low expression of RAB6B, RABL2A, and RABL2B was observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance.
Bladder Cancer Metastasis Induced by Chronic Everolimus Application Can Be Counteracted by Sulforaphane In Vitro
Authors: Justin Saira , Rutz Jochen , Maxeiner Sebastian , Chun Felix K.-H. , Juengel Eva , Blaheta Roman A.
Published: August 2020

Chronic treatment with the mTOR inhibitor, everolimus, fails long-term in preventing tumor growth and dissemination in cancer patients. Thus, patients experiencing treatment resistance seek complementary measures, hoping to improve therapeutic efficacy. This study investigated metastatic characteristics of bladder carcinoma cells exposed to everolimus combined with the isothiocyanate sulforaphane (SFN), which has been shown to exert cancer inhibiting properties. RT112, UMUC3, or TCCSUP bladder carcinoma cells were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 µM), alone or in combination. Adhesion and chemotaxis along with profiling details of CD44 receptor variants (v) and integrin α and β subtypes were evaluated. The functional impact of CD44 and integrins was explored by blocking studies and siRNA knock-down. Long-term exposure to everolimus enhanced chemotactic activity, whereas long-term exposure to SFN or the SFN-everolimus combination diminished chemotaxis. CD44v4 and v7 increased on RT112 cells following exposure to SFN or SFN-everolimus. Up-regulation of the integrins α6, αV, and β1 and down-regulation of β4 that was present with everolimus alone could be prevented by combining SFN and everolimus. Down-regulation of αV, β1, and β4 reduced chemotactic activity, whereas knock-down of CD44 correlated with enhanced chemotaxis. SFN could, therefore, inhibit resistance-related tumor dissemination during everolimus-based bladder cancer treatment.
The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?
Authors: Muthu Manikandan , Chun Sechul , Gopal Judy , Park Gyun-Seok , Nile Arti , Shin Jisoo , Shin Juhyun , Kim Tae-Hyoung , Oh Jae-Wook
Published: August 2020

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.
The Alleviation of Photosynthetic Damage in Tomato under Drought and Cold Stress by High CO2 and Melatonin
Authors: Zhou Rong , Wan Hongjian , Jiang Fangling , Li Xiangnan , Yu Xiaqing , Rosenqvist Eva , Ottosen Carl-Otto
Published: August 2020

The atmospheric CO2 concentration (a[CO2]) is increasing at an unprecedented pace. Exogenous melatonin plays positive roles in the response of plants to abiotic stresses, including drought and cold. The effect of elevated CO2 concentration (e[CO2]) accompanied by exogenous melatonin on plants under drought and cold stresses remains unknown. Here, tomato plants were grown under a[CO2] and e[CO2], with half of the plants pre-treated with melatonin. The plants were subsequently treated with drought stress followed by cold stress. The results showed that a decreased net photosynthetic rate (PN) was aggravated by a prolonged water deficit. The PN was partially restored after recovery from drought but stayed low under a successive cold stress. Starch content was downregulated by drought but upregulated by cold. The e[CO2] enhanced PN of the plants under non-stressed conditions, and moderate drought and recovery but not severe drought. Stomatal conductance (gs) and the transpiration rate (E) was less inhibited by drought under e[CO2] than under a[CO2]. Tomato grown under e[CO2] had better leaf cooling than under a[CO2] when subjected to drought. Moreover, melatonin enhanced PN during recovery from drought and cold stress, and enhanced biomass accumulation in tomato under e[CO2]. The chlorophyll a content in plants treated with melatonin was higher than in non-treated plants under e[CO2] during cold stress. Our findings will improve the knowledge on plant responses to abiotic stresses in a future [CO2]-rich environment accompanied by exogenous melatonin.