bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Single-Cell Technology in the Study and Control of Infectious Diseases
Authors: Lin Weikang Nicholas , Tay Matthew Zirui , Lu Ri , Liu Yi , Chen Chia-Hung , Cheow Lih Feng
Published: June 2020

The advent of single-cell research in the recent decade has allowed biological studies at an unprecedented resolution and scale. In particular, single-cell analysis techniques such as Next-Generation Sequencing (NGS) and Fluorescence-Activated Cell Sorting (FACS) have helped show substantial links between cellular heterogeneity and infectious disease progression. The extensive characterization of genomic and phenotypic biomarkers, in addition to host–pathogen interactions at the single-cell level, has resulted in the discovery of previously unknown infection mechanisms as well as potential treatment options. In this article, we review the various single-cell technologies and their applications in the ongoing fight against infectious diseases, as well as discuss the potential opportunities for future development.
Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
Authors: Krammes Lena , Hart Martin , Rheinheimer Stefanie , Diener Caroline , Menegatti Jennifer , Grässer Friedrich , Keller Andreas , Meese Eckart
Published: June 2020

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration.
Simultaneous Electrodeposition of Silver and Tungsten from [EMIm]Cl:AlCl3 Ionic Liquids outside the Glove Box
Authors: Höhlich Dominik , Mehner Thomas , Scharf Ingolf , Lampke Thomas
Published: June 2020

Ag–W two-phase system was prepared by electrodeposition using anhydrous 1-ethyl-3-methylimidazolium chloride [EMIm]Cl ionic-liquid (IL) solution with AlCl3 in different ratios. The deposition took place outside the glove box with a continuous Ar stream over the electrolyte at 120 °C and a pulsed-like current regime. Resultant layers show areas of Ag and W with an overall W content with a mass fraction of w W   = 50% (mole fraction x W   = 36.9%). The phase composition of Ag–W layers was observed by X-ray diffraction, and the chemical composition was characterized by scanning electron microscopy and inductively coupled plasma optical emission spectroscopy.
Wave Transmission by Rectangular Submerged Breakwaters
Authors: Magdalena Ikha , Atras Muh Fadhel , Sembiring Leo , Nugroho M. A. , Labay Roi Solomon B. , Roque Marian P.
Published: June 2020

In this paper, we investigate the wave damping mechanism caused by the presence of submerged bars using the Shallow Water Equations (SWEs). We first solve these equations for the single bar case using separation of variables to obtain the analytical solution for the wave elevation over a rectangular bar wave reflector with specific heights and lengths. From the analytical solution, we derive the wave reflection and transmission coefficients and determine the optimal height and length of the bar that would give the smallest transmission coefficient. We also measure the effectiveness of the bar by comparing the amplitude of the incoming wave before and after the wave passes the submerged bar, and extend the result to the case of n-submerged bars. We then construct a numerical scheme for the SWEs based on the finite volume method on a staggered grid to simulate the propagation of a monochromatic wave as it passes over a single submerged rectangular bar. For validation, we compare the transmission coefficient values obtained from the analytical solution, numerical scheme, and experimental data. The result of this paper may be useful in wave reflector engineering and design, particularly that of rectangle-shaped wave reflectors, as it can serve as a basis for designing bar wave reflectors that reduce wave amplitudes optimally.
Performance Optimization of a Condenser in Ocean Thermal Energy Conversion (OTEC) System Based on Constructal Theory and a Multi-Objective Genetic Algorithm
Authors: Wu Zhixiang , Feng Huijun , Chen Lingen , Ge Yanlin
Published: June 2020

Constructal optimization of a plate condenser with fixed heat transfer rate and effective volume in ocean thermal energy conversion (OTEC) system is performed based on constructal theory. Optimizations of entropy generation rate ( S ˙ g ) in heat transfer process and total pumping power ( P sum ) due to friction loss are two conflicting objectives for a plate condenser. With the conventional optimization method, the plate condenser is designed by taking a composite function (CF) considering both S ˙ g and P sum as optimization objectives, and employing effective length, width, and effective number of heat transfer plates as design variables. Effects of structural parameters of the plate condenser and weighting coefficient of CF on design results are investigated. With a multi-objective genetic algorithm, the plate condenser is designed by simultaneously optimizing S ˙ g and P sum , and the Pareto optimal set is obtained. The results demonstrate that CFs after primary and twice-constructal optimizations are respectively reduced by 7.8% and 9.9% compared with the initial CF, and the effective volume of the plate condenser has a positive impact on the twice minimum CF. Furthermore, the Pareto optimal set can provide better selections for performance optimizations of plate condensers.
Doing Inventing in the Library. Analyzing the Narrative Framing of Making in a Public Library Context
Authors: Skåland Gro , Arnseth Hans Christian , Pierroux Palmyre
Published: June 2020

In this article, we examine how creative making is framed in a public library setting. We pursue this topic by focusing on the trajectory of a group participating in “The Inventor Course” during a school trip to a library. Video recordings of the maker activity comprise the primary data for analysis, supplemented by ethnographic notes. Analysis of the group’s interactions shows how different frames for inventing are acted out and intersect during the activity. We describe these frames as inventing as invention, inventing as exploration and inventing as narrative. Findings indicate that a narrative frame is a fruitful approach to making in a library setting and that narratives performed in dialogue with children help them to make sense of their explorations.
Knowledge-Based Smart City Service System
Authors: D’Aniello Giuseppe , Gaeta Matteo , Orciuoli Francesco , Sansonetti Giuseppe , Sorgente Francesca
Published: June 2020

A smart city can be defined as a city exploiting information and communication technologies to enhance the quality of life of its citizens by providing them with improved services while ensuring a conscious use of the available limited resources. This paper introduces a conceptual framework for the smart city, namely, the Smart City Service System. The framework proposes a vision of the smart city as a service system according to the principles of the Service-Dominant Logic and the service science theories. The rationale is that the services offered within the city can be improved and optimized via the exploitation of information shared by the citizens. The Smart City Service System is implemented as an ontology-based system that supports the decision-making processes at the government level through reasoning and inference processes, providing the decision-makers with a common operational picture of what is happening in the city. A case study related to the local public transportation service is proposed to demonstrate the feasibility and validity of the framework. An experimental evaluation using the Situation Awareness Global Assessment Technique (SAGAT) has been performed to measure the impact of the framework on the decision-makers’ level of situation awareness.
Vulnerabilities’ Assessment and Mitigation Strategies for the Small Linux Server, Onion Omega2
Authors: Upadhyay Darshana , Sampalli Srinivas , Plourde Bernard
Published: June 2020

The merger of SCADA (supervisory control and data acquisition) and IoTs (internet of things) technologies allows end-users to monitor and control industrial components remotely. However, this transformation opens up a new set of attack vectors and unpredicted vulnerabilities in SCADA/IoT field devices. Proper identification, assessment, and verification of each SCADA/IoT component through advanced scanning and penetration testing tools in the early stage is a crucial step in risk assessment. The Omega2, a small Linux server from Onion™, is used to develop various SCADA/IoT systems and is a key component of nano power grid systems. In this paper, we report product level vulnerabilities of Onion Omega2 that we have uncovered using advanced vulnerability scanning tools. Through this research, we would like to assist vendors, asset owners, network administrators, and security professionals by creating an awareness of the vulnerabilities of Onion Omega2 and by suggesting effective mitigations and security best practices.
Non-Hydropower Renewable Energy in Central Asia: Assessment of Deployment Status and Analysis of Underlying Factors
Authors: Shadrina Elena
Published: June 2020

Despite globally progressing energy transition, the deployment of non-hydropower renewable energy (NHRE) in Central Asia is moderate and varies by country. This paper aims to explain why Central Asian countries with significant challenges in the energy sector are least engaged in NHRE development. In doing so, the paper first reviews scholarly work on renewable energy (RE) deployment in developing countries. For assessing the NHRE development status in Central Asian countries, the paper adopts a two-stage analytical framework. First, it assesses the current situation in these states’ energy sectors in connection to their economic growth and development, environmental sustainability and energy security. Then, it analyses the preparedness of the national energy sectors for NHRE diffusion in six dimensions: structure of energy sector, RE regulation, institutions and governance, capital and investment, infrastructure and business environment, and human capital. Based on the results of the two-stage analysis, the paper argues that more advanced economically and institutionally countries are more likely to commence NHRE development.
Thermo-Fluidic Characterizations of Multi-Port Compact Thermal Model of Ball-Grid-Array Electronic Package
Authors: Bissuel Valentin , Joly Frédéric , Monier-Vinard Eric , Neveu Alain , Daniel Olivier
Published: June 2020

The concept of a single-input/multi-output thermal network was proposed by the Development of Libraries of Physical models for an Integrated design environment (DELPHI) consortium more than twenty years ago. The present work highlights the recent improvements made to efficiently derive a low-computing-effort model from a fully detailed numerical model and to characterize its performances. The temperature predictions of a deduced ball-grid-array (BGA) dynamic compact thermal model are compared to those of a realistic three-dimensional representation, including the large set of internal copper traces, as well as its board structure, which has been validated by experiment. The current study discloses a method for creating an amalgam reduced-order modal model (AROMM) for that electronic component family that allows the preservation of the geometry integrity and shortening scenarios computation. Typically, the AROMM method reduces by a factor of 600 the computation time needed to obtain the solution while keeping the error on the maximum temperature below 2%. Then, a meta-heuristic optimization is run to derive a more practical low-order resistor capacitor model that enables a thermo-fluidic analysis at the board level. Based on the calibrated numerical model, a novel AROMM method was investigated in order to address the chip behavior submitted to multiple heat sources. The first results highlight the capability to enforce a non-uniform power distribution on the upper surface of the silicon chip. Thus, the chip design layout can be analyzed and optimized to prevent thermal and reliability issues.
Fault Diagnosis of PMSG Stator Inter-Turn Fault Using Extended Kalman Filter and Unscented Kalman Filter
Authors: El Sayed Waseem , Abd El Geliel Mostafa , Lotfy Ahmed
Published: June 2020

Since the permeant magnet synchronous generator (PMSG) has many applications in particular safety-critical applications, enhancing PMSG availability has become essential. An effective tool for enhancing PMSG availability and reliability is continuous monitoring and diagnosis of the machine. Therefore, designing a robust fault diagnosis (FD) and fault tolerant system (FTS) of PMSG is essential for such applications. This paper describes an FD method that monitors online stator winding partial inter-turn faults in PMSGs. The fault appears in the direct and quadrature (dq)-frame equations of the machine. The extended Kalman filter (EKF) and unscented Kalman filter (UKF) were used to detect the percentage and the place of the fault. The proposed techniques have been simulated for different fault scenarios using Matlab®/Simulink®. The results of the EKF estimation responses simulation were validated with the practical implementation results of tests that were performed with a prototype PMSG used in the Arab Academy For Science and Technology (AAST) machine lab. The results showed impressive responses with different operating conditions when exposed to different fault states to prevent the development of complete failure.
Performance Analysis of a Novel TCP Protocol Algorithm Adapted to Wireless Networks
Authors: Olmedo Gonzalo , Lara-Cueva Román , Martínez Diego , de Almeida Celso
Published: June 2020

As telecommunication systems evolve towards new-generation architectures, likewise, new protocols are created in order to improve efficiency. One of these protocols is Transmission Control Protocol (TCP), which controls the transmission bit rate in function of network congestion. Nevertheless, in wireless communications, there appear problems such as noise and interference, for which TCP was not designed. Based on these problems, there exist some methods trying to mitigate congestion, such as explicit loss notifications and the use of end-to-end codification. The aim of this work was to propose a wireless TCP protocol improvement, considering a negative acknowledgment (NACK), which allows to differentiate between losses due to congestion and losses due to wireless channel issues. NACK employs a small protocol packet and produces improvement in the quality of service metrics. The experiments were carried out in in-door and out-door environments, over an online video game scenario, and over a long-distance wireless link between two islands. The average results show a 25-percent delay improvement and a 5-percent jitter improvement when compared to the original TCP Reno protocol, while for throughput a 90-percent improvement was achieved for distances between 100 and 414 m.
Improvement of Fatty Acid Profile in Durum Wheat Breads Supplemented with Portulaca oleracea L. Quality Traits of Purslane-Fortified Bread
Authors: Melilli Maria Grazia , Di Stefano Vita , Sciacca Fabiola , Pagliaro Antonella , Bognanni Rosaria , Scandurra Salvatore , Virzì Nino , Gentile Carla , Palumbo Massimo
Published: June 2020

The addition of functional ingredients to breads could have effects on preventing cardiovascular diseases, cancers and inflammation. The incorporation of 0–5–10–15% of three populations of dried purslane flour on the rheological, sensorial and nutritional quality of fortified durum wheat breads were evaluated. The increase in dried purslane (up to 15%) caused an increase in the resistance to the mixture and a consequent reduction in its extensibility. The “panel test” gave a largely positive evaluation in 10% of enrichment. The fatty acids in breads resulted higher with the 5% substitution. Contrary to what has been imagined, the increase in percentage of substitution to 10 and 15% did not lead to an increase in linoleic (omega-3) and α-linolenic (omega-6) acid and probably the cause is in the cooking. The total phenols content and the antioxidant potential, evaluated by ferric reducing antioxidant potential (FRAP) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays of the enriched breads increased with the percentage of the dry purslane substitution. The enrichment of the durum wheat flour with 5% purslane resulted in a good compromise to obtain good rheological characteristics of loaves and breads with decreased omega-6/omega-3 ratio and good antioxidant properties.
New β-Carotene-Chitooligosaccharides Complexes for Food Fortification: Stability Study
Authors: Bockuviene Alma , Sereikaite Jolanta
Published: June 2020

The application of β-carotene in food industry is limited due to its chemical instability. The drawback may be overcome by designing new delivery systems. The stability of β-carotene complexed with chitooligosaccharides by kneading, freeze-drying and sonication methods was investigated under various conditions. The first-order kinetics parameters of the reaction of β-carotene degradation were calculated. The complexation improved the stability of β-carotene at high temperatures and ensured its long-term stability in the dark at 4 °C and 24 °C, and in the light at 24 °C. In water solutions, the best characteristics were exhibited by the complexes prepared by freeze-drying and sonication methods. In the powder form, the complexes retained their colour for the period of the investigation of four months. The calculated total colour differences of the complexes were qualified as appreciable, detectable by ordinary people, but not large. Therefore, β-carotene-chitooligosaccharides complexes could be used as a new delivery system suitable for food fortification.
Amphiphilic Polymer Co-Networks
Authors: Díaz David Díaz
Published: June 2020

Amphiphilic Polymer Co-networks: Synthesis, Properties, Modelling and Applications is a new and very interesting book published by the Royal Society of Chemistry and edited by Prof. Costas S. Patrickios (University of Cyprus). Herein, a brief review of the most important features of the book and its contents is provided from a personal perspective.
Uncorrelated Geo-Text Inhibition Method Based on Voronoi K-Order and Spatial Correlations in Web Maps
Authors: He Yufeng , Sheng Yehua , Jing Yunqing , Yin Yue , Hasnain Ahmad
Published: June 2020

Unstructured geo-text annotations volunteered by users of web map services enrich the basic geographic data. However, irrelevant geo-texts can be added to the web map, and these geo-texts reduce utility to users. Therefore, this study proposes a method to detect uncorrelated geo-text annotations based on Voronoi k-order neighborhood partition and auto-correlation statistical models. On the basis of the geo-text classification and semantic vector transformation, a quantitative description method for spatial autocorrelation was established by the Voronoi weighting method of inverse vicinity distance. The Voronoi k-order neighborhood self-growth strategy was used to detect the minimum convergence neighborhood for spatial autocorrelation. The Pearson method was used to calculate the correlation degree of the geo-text in the convergence region and then deduce the type of geo-text to be filtered. Experimental results showed that for given geo-text types in the study region, the proposed method effectively calculated the correlation between new geo-texts and the convergence region, providing an effective suggestion for preventing uncorrelated geo-text from uploading to the web map environment.
Multifractal Characteristics of Seismogenic Systems and b Values in the Taiwan Seismic Region
Authors: Hui Chun , Cheng Changxiu , Ning Lixin , Yang Jing
Published: June 2020

Seismically active fault zones are complex natural systems and they exhibit multifractal correlation between earthquakes in space and time. In this paper, the seismicity of the Taiwan seismic region was studied through the multifractal characteristics of the spatial-temporal distribution of earthquakes from 1st January 1995 to 1st January 2019. We quantified the multifractal characteristics of Taiwan at different scales and defined them as ΔD values. Furthermore, we studied the relationship between the ΔD and b values, which signifies the average size distribution of those earthquakes. The results are as follows. (1) The temporal multifractal curve changes substantially before and after the strong earthquakes. (2) The maximum ΔD value of the seismic region in Taiwan occurs at depths of 0~9 km, indicating that geological structures and focal mechanisms is the most complex at these depths compared with other depths. (3) ΔD values for different regions range from 0.2~1.5, and b values range from 0.65~1.3, with a significant positive correlation between them (ΔD = 1.5 × b − 0.68). For this purpose, a statistical relationship is developed between b and ΔD values, and regional and temporal changes of these parameters are analyzed in order to reveal the potential of future earthquakes in the study region.
Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
Authors: Gómez-Redondo Isabel , Ramos-Ibeas Priscila , Pericuesta Eva , Fernández-González Raúl , Laguna-Barraza Ricardo , Gutiérrez-Adán Alfonso
Published: June 2020

Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells.
Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy
Authors: Lin Ying-Chun , Chen Yu-Chia , Chen Rui-Yun , Huang Yi-Xuan , Tu Siang-Jyun , Liang Ji-An , Hung Yao-Ching , Yeh Lian-Shung , Chang Wei-Chun , Lin Wu-Chou , Chang Yin-Yi , Chen Shang-Wen , Chang Jan-Gowth
Published: June 2020

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.
SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability
Authors: Yu Miao , Shi Xiaoyan , Ren Mengmeng , Liu Lu , Qi Hao , Zhang Chi , Zou Junhua , Qiu Xiaoyan , Zhu Wei-Guo , Zhang Ying E. , Wang Wengong , Luo Jianyuan
Published: June 2020

Serine-threonine kinase receptor-associated protein (STRAP) functions as a regulator of both TGF-β and p53 signaling that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP acetylation plays an important role in p53-mediated cell cycle arrest and apoptosis. STRAP is acetylated at lysines 147, 148, and 156 by the acetyltransferases CREB-binding protein (CBP) and that the acetylation is reversed by the deacetylase sirtuin7 (SIRT7). Hypo- or hyperacetylation mutations of STRAP at lysines 147, 148, and 156 (3KR or 3KQ) influence its activation and stabilization of p53. Moreover, following 5-fluorouracil (5-FU) treatment, STRAP is mobilized from the cytoplasm to the nucleus and promotes STRAP acetylation. Our finding on the regulation of STRAP links p53 with SIRT7 influencing p53 activity and stability.
Switching Homes: How Cancer Moves to Bone
Authors: Ponzetti Marco , Rucci Nadia
Published: June 2020

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to “switch homes” and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of “vicious cycle” and “osteolytic” vs. “osteosclerotic” bone metastases; as well as on novel concepts, such as cellular dormancy and extracellular vesicles. At the molecular level, we will focus on hypoxia-associated factors and angiogenesis, the Wnt pathway, parathyroid hormone-related peptide (PTHrP) and chemokines. At the supramolecular/cellular level, we will discuss tumour dormancy, id est the mechanisms through which a small contingent of tumour cells coming from the primary site may be kept dormant in the endosteal niche for many years. Finally, we will present a potential role for the multimolecular mediators known as extracellular vesicles in determining bone-tropism and establishing a premetastatic niche by influencing the bone microenvironment.
Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases
Authors: Lin Yu-Lung , Lin Yi-Wei , Nhieu Jennifer , Zhang Xiaoyin , Wei Li-Na
Published: June 2020

Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SODG93A or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of Crabp1 by Shh. In SODG93A or AR-65Q MN1 neurons, CRABP1 level is reduced, revealing a correlation of motor neuron degeneration with Crabp1 down-regulation. Up-regulation of Crabp1 by Shh is mediated by glioma-associated oncogene homolog 1 (Gli1) that binds the Gli target sequence in Crabp1′s neuron-specific regulatory region upstream of minimal promoter. Gli1 binding triggers chromatin juxtaposition with minimal promoter, activating transcription. Motor neuron differentiation and Crabp1 up-regulation are both inhibited by blunting Shh with Gli inhibitor GANT61. Expression data mining of ALS and spinal muscular atrophy (SMA) motor neurons shows reduced CRABP1, coincided with reduction in Shh-Gli1 signaling components. This study reports motor neuron degeneration correlated with down-regulation in Crabp1 and Shh-Gli signaling. Shh-Gli up-regulation of Crabp1 involves specific chromatin remodeling. The physiological and pathological implication of this regulatory pathway in motor neuron degeneration is supported by gene expression data of ALS and SMA patients.
Comprehensive Bioinformatics Identifies Key microRNA Players in ATG7-Deficient Lung Fibroblasts
Authors: Stojanović Stevan D. , Fuchs Maximilian , Fiedler Jan , Xiao Ke , Meinecke Anna , Just Annette , Pich Andreas , Thum Thomas , Kunz Meik
Published: June 2020

Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.
Co-Culturing of Endothelial and Cancer Cells in a Nanofibrous Scaffold-Based Two-Layer System
Authors: Oh Ye-Seul , Choi Min-Ho , Shin Jung-In , Maza Perry Ayn Mayson A. , Kwak Jong-Young
Published: June 2020

Angiogenesis is critical for local tumor growth. This study aimed to develop a three-dimensional two-layer co-culture system to investigate effects of cancer cells on the growth of endothelial cells (ECs). Poly(ε-caprolactone) (PCL) nanofibrous membranes were generated via electrospinning of PCL in chloroform (C-PCL-M) and chloroform and dimethylformamide (C/DMF-PCL-M). We assembled a two-layer co-culture system using C-PCL-M and C/DMF-PCL-M for EC growth in the upper layer with co-cultured cancer cells in the lower layer. In the absence of vascular endothelial growth factor (VEGF), growth of bEND.3 ECs decreased on C/DMF-PCL-M but not on C-PCL-M with time. Growth of bEND.3 cells on C/DMF-PCL-M was enhanced through co-culturing of CT26 cancer cells and enhanced growth of bEND.3 cells was abrogated with anti-VEGF antibodies and sorafenib. However, EA.hy926 ECs displayed steady growth and proliferation on C/DMF-PCL-M, and their growth was not further increased through co-culturing of cancer cells. Moreover, chemical hypoxia in CT26 cancer cells upon treatment with CoCl2 enhanced the growth of co-cultured bEND.3 cells in the two-layer system. Thus, EC growth on the nanofibrous scaffold is dependent on the types of ECs and composition of nanofibers and this co-culture system can be used to analyze EC growth induced by cancer cells.
MnTBAP Reverses Pulmonary Vascular Remodeling and Improves Cardiac Function in Experimentally Induced Pulmonary Arterial Hypertension
Authors: Gomez-Puerto Maria Catalina , Sun Xiao-Qing , Schalij Ingrid , Orriols Mar , Pan Xiaoke , Szulcek Robert , Goumans Marie-José , Bogaard Harm-Jan , Zhou Qian , ten Dijke Peter
Published: June 2020

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by obstructed pulmonary vasculatures. Current therapies for PAH are limited and only alleviate symptoms. Reduced levels of BMPR2 are associated with PAH pathophysiology. Moreover, reactive oxygen species, inflammation and autophagy have been shown to be hallmarks in PAH. We previously demonstrated that MnTBAP, a synthetic metalloporphyrin with antioxidant and anti-inflammatory activity, inhibits the turn-over of BMPR2 in human umbilical vein endothelial cells. Therefore, we hypothesized that MnTBAP might be used to treat PAH. Human pulmonary artery endothelial cells (PAECs), as well as pulmonary microvascular endothelial (MVECs) and smooth muscle cells (MVSMCs) from PAH patients, were treated with MnTBAP. In vivo, either saline or MnTBAP was given to PAH rats induced by Sugen 5416 and hypoxia (SuHx). On PAECs, MnTBAP was found to increase BMPR2 protein levels by blocking autophagy. Moreover, MnTBAP increased BMPR2 levels in pulmonary MVECs and MVSMCs isolated from PAH patients. In SuHx rats, MnTBAP reduced right ventricular (RV) afterload by reversing pulmonary vascular remodeling, including both intima and media layers. Furthermore, MnTBAP improved RV function and reversed RV dilation in SuHx rats. Taken together, these data highlight the importance of MnTBAP as a potential therapeutic treatment for PAH.
The Role of Sugars in the Regulation of the Level of Endogenous Signaling Molecules during Defense Response of Yellow Lupine to Fusarium oxysporum
Authors: Formela-Luboińska Magda , Chadzinikolau Tamara , Drzewiecka Kinga , Jeleń Henryk , Bocianowski Jan , Kęsy Jacek , Labudda Mateusz , Jeandet Philippe , Morkunas Iwona
Published: June 2020

Soluble sugars such as sucrose, glucose and fructose in plant host cells not only play the role as donors of carbon skeletons, but they may also induce metabolic signals influencing the expression of defense genes. These metabolites function in a complex network with many bioactive molecules, which independently or in dialogue, induce successive defense mechanisms. The aim of this study was to determine the involvement of sucrose and monosaccharides as signaling molecules in the regulation of the levels of phytohormones and hydrogen peroxide participating in the defense responses of Lupinus luteus L. to a hemibiotrophic fungus Fusarium oxysporum Schlecht f. sp. lupini. A positive correlation between the level of sugars and postinfection accumulation of salicylic acid and its glucoside, as well as abscisic acid, was noted. The stimulatory effect of sugars on the production of ethylene was also reported. The protective role of soluble sugars in embryo axes of yellow lupine was seen in the limited development of infection and fusariosis. These results provide evidence for the enhanced generation of signaling molecules both by sugar alone as well as during the crosstalk between sugars and infection caused by F. oxysporum. However, a considerable postinfection increase in the level of these signaling molecules under the influence of sugars was recorded. The duration of the postinfection generation of these molecules in yellow lupine was also variable.
Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats
Authors: Kidani Naoya , Hishikawa Tomohito , Hiramatsu Masafumi , Nishihiro Shingo , Kin Kyohei , Takahashi Yu , Murai Satoshi , Sugiu Kenji , Yasuhara Takao , Miyazaki Ikuko , Asanuma Masato , Date Isao
Published: June 2020

Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for “oxidative phosphorylation” was significantly upregulated while fourteen other gene sets including “apoptosis”, “hypoxia” and “reactive oxygen species” showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.
Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
Authors: Just Katja S. , Dormann Harald , Schurig Marlen , Böhme Miriam , Fracowiak Jochen , Steffens Michael , Scholl Catharina , Seufferlein Thomas , Gräff Ingo , Schwab Matthias , Stingl Julia C.
Published: June 2020

Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (n = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel (p = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73−14.27)), together with age (1.05 (1.02−1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs (p = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.
The Enemy Which Sealed the World: Effects of COVID-19 Diffusion on the Psychological State of the Italian Population
Authors: Forte Giuseppe , Favieri Francesca , Tambelli Renata , Casagrande Maria
Published: June 2020

Background: Starting from the first months of 2020, worldwide population has been facing the COVID-19 pandemic. Many nations, including Italy, took extreme actions to reduce the diffusion of the virus, profoundly changing lifestyles. The Italians have been faced with both the fear of contracting the infection and the consequences of enforcing social distancing. This study was aimed to understand the psychological impact of the COVID-19 outbreak and the psychopathological outcomes related to the first phase of this emergency. Methods: The study included 2291 respondents. An online survey collected information on socio-demographic variables, history of direct or indirect contact with COVID-19, and additional information concerning the COVID-19 emergency. Moreover, psychopathological symptoms such as anxiety, mood alterations and post-traumatic symptomatology were assessed. Results: The results revealed that respectively 31.38%, 37.19% and 27.72% of respondents reported levels of general psychopathological symptomatology, anxiety, and PTSD symptoms over the cut-off scores. Furthermore, a significant worsening of mood has emerged. Being a female or under the age of 50 years, having had direct contact with people infected by the COVID-19, and experiencing uncertainty about the risk of contagion represent risk factors for psychological distress. Conclusions: Our findings indicate that the first weeks of the COVID-19 pandemic appear to impact not only on physical health but also on psychological well-being. Although these results need to be considered with caution being based on self-reported data collected at the beginning of this emergency, they should be used as a starting point for further studies aimed to develop interventions to minimize both the brief and long-term psychological consequences of the COVID-19 pandemic.
Disability of Dialysis Patients and the Condition of Blood Vessels
Authors: Gołębiowski Tomasz , Kusztal Mariusz , Konieczny Andrzej , Letachowicz Krzysztof , Gawryś Ada , Skolimowska Beata , Ostrowska Bożena , Zmonarski Sławomir , Janczak Dariusz , Krajewska Magdalena
Published: June 2020

The number of elderly hemodialysis patients is constantly increasing worldwide. This population has a high burden of comorbid conditions, which impair daily activities. The aim of the study was to analyze problems of disability in hemodialysis patients in the context of cardiovascular (CV) complications and vascular condition. In this cross-sectional study, 129 patients (mean age 64.5) were enrolled. The degree of disability in Barthel index (Bi) and 10-year cardiovascular risk (QRISK®3) were assessed. A Mobil-O-Graph monitor was used for measuring hemodynamic parameters. Only 6.2% of patients were professionally active, 19% used a wheelchair for transport, and 16% used crutches. More than half (51%) were independent in everyday activities reaching 80–100 points on Bi. The rest, with Bi < 80, were considered as dependent. The most common causes of disability were CV complications. The independent group (80–100 points) was characterized by significantly lower pulse wave velocity (PWV) and lower QRISK®3 compared to dependent patients. The degree of disability negatively correlated with age, PWV, and QRISK®3. Multivariate logistic regression revealed that disability (Bi < 80) was independently associated with CV events in the past adjusted odds ratio (adj.OR) 4.83 (95% confidence interval (95% CI): 1.74–13.41) and higher PWV adj.OR 1.45 (95% CI: 1.15–1.82). Our results indicate that CV diseases are the most important cause of functional impairment.
Progress of Bio-Calcium Carbonate Waste Eggshell and Seashell Fillers in Polymer Composites: A Review
Authors: Owuamanam Stephen , Cree Duncan
Published: June 2020

Disposal of massive amounts of eggshells and seashells from processing industries is a challenge. In recent years, there has been a focus to reuse these waste resources in the production of new thermoplastic and thermoset polymer materials. This paper reviews eggshell and seashell production by country and provides a perspective on the quantity of bio-calcium carbonate that could be produced annually from these wastes. The achievements obtained from the addition of recycled bio-calcium carbonate fillers (uncoated/unmodified) in polymer composites with a focus on tensile strength, flexural strength and impact toughness are discussed. To improve compatibility between calcium carbonate (mineral and bio-based) fillers and polymers, studies on surface modifiers are reviewed. Knowledge gaps and future research and development thoughts are outlined. Developing novel and innovative composites for this waste material could bring additional revenue to egg and seafood processors and at the same time reduce any environmental impact.
The Effects of Short-Term High-Intensity Interval Training and Moderate Intensity Continuous Training on Body Fat Percentage, Abdominal Circumference, BMI and VO2max in Overweight Subjects
Authors: Russomando Luca , Bono Vincenzo , Mancini Annamaria , Terracciano Alessia , Cozzolino Francesca , Imperlini Esther , Orrù Stefania , Alfieri Andreina , Buono Pasqualina
Published: June 2020

We aimed to compare the effects of a personalized short-term high-intensity interval training (HIIT) vs. standard moderate intensity continuous training (MICT) on body fat percentage, abdominal circumference, BMI and maximal oxygen uptake (VO2max) in overweight volunteers. Twenty overweight sedentary volunteers (24.9 ± 2.9y; BMI: 26.1 ± 1 kgm−2) were randomly assigned to 2 groups, HIIT or MICT. HIIT trained 6 weeks (3-days/week), 40-min sessions as follows: 6-min warm-up, 20-min resistance training (RT) at 70% 1-RM, 8-min HIIT up to 90% of the predicted Maximal Heart Rate (HRmax), 6-min cool-down. MICT trained 6 weeks (3-days/week) 60-min sessions as follows: 6-min warm-up, 20-min RT at 70% 1-RM, 30-min MICT at 60–70% of the predicted HRmax, 4-min cool-down. Two-way ANOVA was performed in order to compare the efficacy of HIIT and MICT protocols, and no significant interaction between training x time was evidenced (p > 0.05), indicating similar effects of both protocols on all parameters analyzed. Interestingly, the comparison of Δ mean percentage revealed an improvement in VO2max (p = 0.05) together with a positive trend in the reduction of fat mass percentage (p = 0.06) in HIIT compared to MICT protocol. In conclusion, 6 weeks of personalized HIIT, with reduced training time (40 vs. 60 min)/session and volume of training/week, improved VO2max and reduced fat mass percentage more effectively compared to MICT. These positive results encourage us to test this training in a larger population.