bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication
Authors: Gou Hongchao , Bian Zhibiao , Li Yan , Cai Rujian , Jiang Zhiyong , Song Shuai , Zhang Kunli , Chu Pinpin , Yang Dongxia , Li Chunling
Published: January 2021

For viral replication to occur in host cells, low-molecular-weight metabolites are necessary for virion assembly. Recently, metabolomics has shown great promise in uncovering the highly complex mechanisms associated with virus-host interactions. In this study, the metabolic networks in PK-15 cells infected with a variant virulent or classical attenuated pseudorabies virus (PRV) strains were explored using gas chromatography-mass spectrometry (GC-MS) analysis. Although total numbers of metabolites whose levels were altered by infection with the variant virulent strain or the classical attenuated strain were different at 8 and 16 h post infection (hpi), the predicted levels of differential metabolic components were shown to be associated with specific pathways, including glycolysis as well as amino acid and nucleotide metabolism. The glucose depletion and glycolysis inhibitors 2DG and oxamate could reduce the level of PRV replication in PK-15 cells. In addition, the inhibition of the pentose phosphate pathway (PPP) resulted in an obvious decline of viral titers, but the prevention of oxidative phosphorylation in the tricarboxylic acid (TCA) cycle had a minimal effect on viral replication. Glutamine starvation resulted in the decline of viral titers, which could be restored by supplemental addition in the culture media. However, inhibition of glutaminase (GLS) activity or the supplement of 2-ketoglutarate into glutamine-deleted DMEM did not alter PRV replication in PK-15 cells. The results of the current study indicate that PRV reprograms the metabolic activities of PK-15 cells. The metabolic flux from glycolysis, PPP and glutamine metabolism to nucleotide biosynthesis was essential for PRV to enhance its replication. This study will help to identify the biochemical materials utilized by PRV replication in host cells, and this knowledge can aid in developing new antiviral strategies.
On the Optimization of a Multimodal Electromagnetic Vibration Energy Harvester Using Mode Localization and Nonlinear Dynamics
Authors: Aouali Kaouthar , Kacem Najib , Bouhaddi Noureddine , Haddar Mohamed
Published: January 2021

In this paper we study a generic model of a nonlinear quasiperiodic vibration energy harvester (VEH) based on electromagnetic transduction. The proposed device consists of multiple moving magnets guided by elastic beams and coupled by repulsive magnetic forces. A system of two degrees-of-freedom (DOFs) with tunable nonlinearity and mode localization is experimentally validated. The validated 2-DOFs harvester is optimized using a multiobjective optimization procedure to improve its harvested power and frequency bandwidth. An efficient criterion using the modal kinetic energy of the finite element model is proposed to quantify the energy localized in the structure perturbed zones. Afterward, this concept has been generalized to a 5-DOFs VEH with two perturbed DOFs oscillators and the optimal performances are derived using a multiobjective optimization. This proposed model enables a significant increase in the harvested power and frequency bandwidth by 101% and 79%, respectively, compared to that of the 2-DOFs device. Moreover, it has been shown that harvesting energy from two perturbed magnets among five provides almost the same amount of harvested energy and enhances the frequency bandwidth by 18% compared to those of the periodic system. Consequently, the harvester can be improved by reducing the transduction circuits number and the manufacturing cost.
Validation of a Simulation Tool for an Environmentally Friendly Aircraft Cargo Fire Protection System
Authors: Pathak Arnav , Norrefeldt Victor , Pschirer Marie
Published: January 2021

One of the objectives of the CleanSky-2 project is to develop an Environmentally Friendly Fire Protection (EFFP) system to substitute halon for the aircraft cargo hold. For this, an aircraft demonstrator including the cargo hold was equipped with a nitrogen-based fire suppression system. The demonstrator is located in the Flight Test Facility (FTF) low-pressure vessel and can thus be subjected to realistic cruise pressure conditions and take-off and descent pressure profiles. As a design tool, a zonally refined simulation model to predict the local oxygen and nitrogen concentration distribution in the cargo hold has been developed using the Indoor Environment Simulation Suite (IESS). The model allows for fast transient simulations of the suppression system operation. This paper presents a model validation case of knockdown during cruising, followed by a holding phase and descent.
The Effect of Methyl Anthranilate-Based Repellent on Chemical Composition and Selected Physiological Parameters of Sweet Cherry (Prunus avium L.)
Authors: Mikiciuk Grzegorz , Chełpiński Piotr , Mikiciuk Małgorzata , Możdżer Ewa , Telesiński Arkadiusz
Published: January 2021

Maturing sweet cherry fruits are exposed to damage caused by birds. In order to repel birds from orchards, it is increasingly common to use repellents based on plant extracts and compounds that undergo complete biodegradation. One such compound is methyl anthranilate (2-aminobenzoic acid methyl ester), which has an irritating effect on birds’ senses of taste and smell. The objective of this study was to assess the effect of methyl anthranilate-based repellent (commercial name: Goose Chase/Fruit Shield) on the chemical composition and selected physiological parameters of sweet cherry cv. ‘Burlat’. The repellent containing methyl anthranilate (26.4%) was applied in the form of a foliar spray seven days prior to fruit harvest at a 1% concentration (500 dm3∙ha−1 of working liquid). In the study, methyl anthranilate-based repellent was found to have no influence on the chemical composition of fruits and leaves or the selected physiological parameters of sweet cherry cv. ‘Burlat’. Moreover, the use of methyl anthranilate did not affect the cracking susceptibility of sweet cherry fruits. This compound may constitute an interesting alternative to support sweet cherry orchard protection against birds and in organic cultures.
Antimicrobial Use in Companion Animals: Assessing Veterinarians’ Prescription Patterns through the First National Survey in Chile
Authors: Galarce Nicolás , Arriagada Gabriel , Sánchez Fernando , Venegas Vladimir , Cornejo Javiera , Lapierre Lisette
Published: January 2021

Although the relationship between the use of antimicrobials and the development of resistant bacteria is well established, information about the use of antimicrobials in companion animals has been poorly described, which represents a risk to public health. The aim of this study was to describe the antimicrobial prescription patterns of Chilean companion animal veterinarians. A nationally distributed survey targeted at companion animal veterinarians was designed. The survey included questions about the veterinarian’s demographics, bacterial diseases treated, prescribed antimicrobials, and the use of laboratory diagnostic tools. Three hundred twenty-three responses were collected, most of the respondents were female (59.4%). The most frequently reported bacterial diseases were pyoderma (17.2%), followed by otitis and abscesses (7.4%). The antimicrobials most used corresponded with critically or highly important drugs for veterinary and human use, including β-lactams (65.3%), quinolones (36.2%) and tetracyclines (23.2%). Only 15% of the veterinarians reported the use of laboratory diagnostic tests, although 67% declared they were aware of the official antimicrobial classification schemes. Our results describe for the first time the usage of antimicrobials by veterinarian practitioners in Chile to treat different diseases in companion animals. The data presented here provide a baseline that could help to promote the implementation of clinical guidelines and regulations in order to improve current treatments.
Preventive Effects of Anthraquinones Isolated from an Endophytic Fungus, Colletotrichum sp. JS-0367 in Tumor Necrosis Factor-α-Stimulated Damage of Human Dermal Fibroblasts
Authors: Lee Sullim , Nguyen Quynh Nhu , Phung Hung Manh , Shim Sang Hee , Kim Daeyoung , Hwang Gwi Seo , Kang Ki Sung
Published: January 2021

Reactive oxygen species (ROS) are a major causative factor of inflammatory responses and extracellular matrix degradation. ROS also cause skin aging and diverse cutaneous lesions. Therefore, antioxidants that inhibit the generation of ROS may be beneficial in the relief of skin aging and diseases. We investigated the anti-skin aging effect of anthraquinones from cultures of Colletotrichum sp., an endophytic fungus isolated from Morus alba L. using human dermal fibroblasts (HDFs). We preferentially evaluated the preventive effects of anti-oxidative anthraquinones (1, 4) against the generation of ROS, nitric oxide (NO), and prostaglandins-E2 (PGE2). Among them, 1,3-dihydroxy-2,8-dimethoxy-6-methylanthraquinone (1) suppressed the generation of ROS, NO, and PGE2 in tumor necrosis factor-alpha (TNF-α)-stimulated HDFs. Compound 1 reversed the TNF-induced increase in matrix metalloproteinase (MMP)-1 and a decrease in procollagen I α1 (COLIA1). It also suppressed inducible NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8, which upregulate inflammatory reactions. Mechanistically, compound 1 suppressed nuclear factor-κB, activator protein 1, and mitogen-activated protein kinases in TNF-α-stimulated HDFs. These results suggest that compound 1 may be beneficial for improving skin aging and diverse cutaneous lesions.
The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders
Authors: Vona Rosa , Pallotta Lucia , Cappelletti Martina , Severi Carola , Matarrese Paola
Published: January 2021

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies
Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats
Authors: Hasanein Parisa , Rahdar Abbas , Barani Mahmood , Baino Francesco , Yari Siamak
Published: January 2021

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future.
A Fast Method for Calculation of Marine Gravity Anomaly
Authors: Fang Yuan , He Shuiyuan , Meng Xiaohong , Wang Jun , Gan Yongkang , Tang Hanhan
Published: January 2021

Gravity data have been playing an important role in marine exploration and research. However, obtaining gravity data over an extensive marine area is expensive and inefficient. In reality, marine gravity anomalies are usually calculated from satellite altimetry data. Over the years, numerous methods have been presented for achieving this purpose, most of which are time-consuming due to the integral calculation over a global region and the singularity problem. This paper proposes a fast method for the calculation of marine gravity anomalies. The proposed method introduces a novel scheme to solve the singularity problem and implements the parallel technique based on a graphics processing unit (GPU) for fast calculation. The details for the implementation of the proposed method are described, and it is tested using the geoid height undulation from the Earth Gravitational Model 2008 (EGM2008). The accuracy of the presented method is evaluated by comparing it with marine shipboard gravity data. Its efficiency is demonstrated through comparison with the conventional sequential method. The tests demonstrate that the proposed method can be employed for accurately calculating marine gravity anomalies and provides an advantage on computational efficiency.
Analysing Mouse Skin Cell Behaviour under a Non-Thermal kHz Plasma Jet
Authors: Jurov Andrea , Kos Špela , Hojnik Nataša , Sremački Ivana , Nikiforov Anton , Leys Christophe , Serša Gregor , Cvelbar Uroš
Published: January 2021

Plasma jets are extensively used in biomedical applications, particularly for exploring cell viability behaviour. However, many experimental parameters influence the results, including jet characteristics, secondary liquid chemistry and protocols used, slowing research progress. A specific interest of the presented research was skin cell behaviour under a non-thermal kHz plasma jet—a so-called cold plasma jet—as a topical skin treatment. Our research was focused on in vitro mouse skin cell direct plasma treatment with argon as an operating gas. The research was complemented with detailed gas-phase diagnostics and liquid-phase chemical analysis of the plasma and plasma-treated medium, respectively. The obtained results showed that direct plasma jet treatment was very destructive, leading to low cell viability. Even with short treatment times (from 35 s to 60 s), apoptosis was observed for most L929 murine fibroblasts under approximately the same conditions. This behaviour was attributed to plasma species generated from direct treatment and the types of cell lines used. Importantly, the research exposed important points that should be taken under consideration for all further research in this field: the urgent need to upgrade and standardise existing plasma treatment protocols of cell lines; to monitor gas and liquid chemistries and to standardise plasma discharge parameters.
Antibacterial Behavior of Chitosan-Sodium Hyaluronate-PEGDE Crosslinked Films
Authors: Chuc-Gamboa Martha Gabriela , Cámara Perera Carolina María , Aguilar Ayala Fernando Javier , Vargas-Coronado Rossana Faride , Cauich-Rodríguez Juan Valerio , Escobar-García Diana María , Sánchez-Vargas Luis Octavio , Pacheco Neith , San Román del Barrio Julio
Published: January 2021

Chitosan is a natural polymer that can sustain not only osteoblast adhesion and proliferation for bone regeneration purposes, but it is also claimed to exhibit antibacterial properties towards several Gram-positive and Gram-negative bacteria. In this study, chitosan was modified with sodium hyaluronate, crosslinked with polyethylene glycol diglycidyl ether (PEGDE) and both osteoblast cytotoxicity and antibacterial behavior studied. The presence of sodium hyaluronate and PEGDE on chitosan was detected by FTIR, XRD, and XPS. Chitosan (CHT) films with sodium hyaluronate crosslinked with PEGDE showed a better thermal stability than pristine hyaluronate. In addition, osteoblast cytocompatibility improved in films containing sodium hyaluronate. However, none of the films exhibit antimicrobial activity against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus while exhibiting low to mild activity against Salmonella typhimurion.
Learning to Localise Automated Vehicles in Challenging Environments Using Inertial Navigation Systems (INS)
Authors: Onyekpe Uche , Palade Vasile , Kanarachos Stratis
Published: January 2021

An approach based on Artificial Neural Networks is proposed in this paper to improve the localisation accuracy of Inertial Navigation Systems (INS)/Global Navigation Satellite System (GNSS) based aided navigation during the absence of GNSS signals. The INS can be used to continuously position autonomous vehicles during GNSS signal losses around urban canyons, bridges, tunnels and trees, however, it suffers from unbounded exponential error drifts cascaded over time during the multiple integrations of the accelerometer and gyroscope measurements to position. More so, the error drift is characterised by a pattern dependent on time. This paper proposes several efficient neural network-based solutions to estimate the error drifts using Recurrent Neural Networks, such as the Input Delay Neural Network (IDNN), Long Short-Term Memory (LSTM), Vanilla Recurrent Neural Network (vRNN), and Gated Recurrent Unit (GRU). In contrast to previous papers published in literature, which focused on travel routes that do not take complex driving scenarios into consideration, this paper investigates the performance of the proposed methods on challenging scenarios, such as hard brake, roundabouts, sharp cornering, successive left and right turns and quick changes in vehicular acceleration across numerous test sequences. The results obtained show that the Neural Network-based approaches are able to provide up to 89.55% improvement on the INS displacement estimation and 93.35% on the INS orientation rate estimation.
Carbon Nanotube-Based Composite Filaments for 3D Printing of Structural and Conductive Elements
Authors: Podsiadły Bartłomiej , Matuszewski Piotr , Skalski Andrzej , Słoma Marcin
Published: January 2021

In this publication, we describe the process of fabrication and the analysis of the properties of nanocomposite filaments based on carbon nanotubes and acrylonitrile butadiene styrene (ABS) polymer for fused deposition modeling (FDM) additive manufacturing. Polymer granulate was mixed and extruded with a filling fraction of 0.99, 1.96, 4.76, 9.09 wt.% of CNTs (carbon nanotubes) to fabricate composite filaments with a diameter of 1.75 mm. Detailed mechanical and electrical investigations of printed test samples were performed. The results demonstrate that CNT content has a significant influence on mechanical properties and electrical conductivity of printed samples. Printed samples obtained from high CNT content composites exhibited an improvement in the tensile strength by 12.6%. Measurements of nanocomposites’ electrical properties exhibited non-linear relation between the supply voltage and measured sample resistivity. This effect can be attributed to the semiconductor nature of the CNT functional phase and the occurrence of a tunnelling effect in percolation network. Detailed I–V characteristics related to the amount of CNTs in the composite and the supply voltage influence are also presented. At a constant voltage value, the average resistivity of the printed elements is 2.5 Ωm for 4.76 wt.% CNT and 0.15 Ωm for 9.09 wt.% CNT, respectively. These results demonstrate that ABS/CNT composites are a promising functional material for FDM additive fabrication of structural elements, but also structural electronics and sensors.
Performance Study of Grass-Derived Nano-Cellulose and Polycaprolactone Composites for 3D Printing
Authors: Feng Chen , Zhou Jiping , Xu Xiaodong , Jiang Yani , Shi Hongcan , Zhao Guoqi
Published: January 2021

In recent years, 3D printing has received increasing attention from researchers. This technology overcomes the limitations of traditional technologies by printing precise and personalized scaffold with arbitrary shapes, pore structures, and porosities for the applications in various tissues. The cellulose nanocrystal (CNC) is extracted from Humulus Japonicus (HJS) and mixed with poly(ε-caprolactone) (PCL) to prepare a series of CNC/PCL composites for printing. Based on the analysis of the physical and chemical properties of the series of the CNC/PCL composites, an optimal mass ratio of CNC to PCL was obtained. The Solidworks was used to simulate the stretching and compression process of the scaffolds with three different patterns under an external force. The flow of nutrient solution in the scaffolds with different patterns was simulated by ANSYS FLUENT, and then a new optimization scaffold pattern with a concave hexagon shape was advised based on the simulation results. Collectively, the mechanical test results of the material and scaffold confirmed that the optimal filling amount of the CNC was 5%, and the scaffold pattern with concave hexagon shape exhibited better mechanical properties and suitable for the transport of cells and nutrients, which is expected to be more widely used in 3D printing.
Bi-Level Dispatch and Control Architecture for Power System in China Based on Grid-Friendly Virtual Power Plant
Authors: Xu Qingwen , Cao Yongji , Zhang Hengxu , Zhang Wen , Terzija Vladimir
Published: January 2021

Non-synchronous renewable energy sources (RESs) have strong volatility and low inertia, which brings about great challenges on the accommodation of RESs and the security and stability of power systems. This paper proposes a bi-level power system dispatch and control architecture based on the grid-friendly virtual power plant (GVPP), so as to accommodate RESs flexibly and securely. The typical dispatch and control system of the power system in China is presented, and the particular challenges stemming from non-synchronous RESs are analyzed. The functional requirements, concept, and fundamental design of the GVPP are provided, which is distinguished from traditional virtual power plants (VPPs) for its active participation in power system stability control. Based on the cloud platform, a bi-level dispatch and control architecture considering two objectives is established. First, in the inner level, the GVPP operates to promote the accommodation of RESs under normal condition. Then, from the perspective of out-level power systems, GVPPs serve as spinning reserves for power support under contingencies. Besides, the key problems to be solved in the development of the GVPP-based architecture are summarized. Although the architecture is proposed for the power system in China, it can be applied to any power systems with similar challenges.
Analysis of the Driving Altitude and Ambient Temperature Impact on the Conversion Efficiency of Oxidation Catalysts
Authors: Serrano José Ramón , Piqueras Pedro , Sanchis Enrique José , Diesel Bárbara
Published: January 2021

Worldwide emission standards are extending their requirements to cover engine operation under extreme ambient conditions and fill the gap between the type-approval and real driving conditions. The new ambient boundaries affect the engine performance and raw emissions as well as the efficiency of the exhaust aftertreatment systems. This study evaluates the impact of high altitude and low ambient temperature on the light-off temperature and conversion efficiency of an oxidation catalyst. The results are compared in a common range of exhaust mass flow and temperature with the baseline sea-level operation at 20 °C. A reduction of CO and HC conversion efficiencies was found at 2500 m and −7 °C, with a relevant increase of the light-off temperature for both of the pollutants. The analysis of the experimental data was complemented with the use of a catalyst model to identify the causes leading to the deterioration of the CO and HC light-off. The use of the model allowed for identifying, for the same exhaust mass flow and temperature, the contributions to the variation of conversion efficiency caused by the change in engine-out emissions and tailpipe pressure, which are, in turn, manifested in the variation of the reactants partial pressure and dwell time as governing parameters.
Plasma Concentrations of Extracellular Vesicles Are Decreased in Patients with Post-Infarct Cardiac Remodelling
Authors: Gąsecka Aleksandra , Pluta Kinga , Solarska Katarzyna , Rydz Bartłomiej , Eyileten Ceren , Postula Marek , van der Pol Edwin , Nieuwland Rienk , Budnik Monika , Kochanowski Janusz , Jaguszewski Miłosz J. , Szarpak Łukasz , Mazurek Tomasz , Kapłon-Cieślicka Agnieszka , Opolski Grzegorz , Filipiak Krzysztof J.
Published: January 2021

Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endothelial cells (CD146+), erythrocytes (CD235a+), leukocytes (CD45+), platelets (CD61+), activated platelets (P-selectin+), and EVs exposing phosphatidylserine after AMI were determined by flow cytometry in 55 patients with the first AMI. LVR was defined as an increase in left ventricular end-diastolic volume by 20% at 6 months after AMI, compared to baseline. Results, baseline concentrations of EVs from endothelial cells, erythrocytes and platelets were lower in patients who developed LVR (p ≤ 0.02 for all). Concentrations of EVs from endothelial cells and erythrocytes were independent LVR predictors (OR 8.2, CI 1.3–54.2 and OR 17.8, CI 2.3–138.6, respectively) in multivariate analysis. Combining the three EV subtypes allowed to predict LVR with 83% sensitivity and 87% specificity. Conclusions, decreased plasma concentrations of EVs from endothelial cells, erythrocytes and platelets predict LVR after AMI. Since EV release EVs contributes to cellular homeostasis by waste removal, decreased concentrations of EVs may indicate dysfunctional cardiac homeostasis after AMI, thus promoting LVR.
Knockout of myoc Provides Evidence for the Role of Myocilin in Zebrafish Sex Determination Associated with Wnt Signalling Downregulation
Authors: Atienzar-Aroca Raquel , Aroca-Aguilar José-Daniel , Alexandre-Moreno Susana , Ferre-Fernández Jesús-José , Bonet-Fernández Juan-Manuel , Cabañero-Varela María-José , Escribano Julio
Published: January 2021

Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known as the first glaucoma gene. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 h post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but, remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provides in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination.
Aortic Aneurysms, Chronic Kidney Disease and Metalloproteinases
Authors: Andreucci Michele , Provenzano Michele , Faga Teresa , Michael Ashour , Patella Gemma , Mastroroberto Pasquale , Serraino Giuseppe Filiberto , Bracale Umberto Marcello , Ielapi Nicola , Serra Raffaele
Published: January 2021

Metalloproteinases (MPs) are proteolytic enzymes involved in extracellular matrix deposition, regulation of cellular signals of inflammation, proliferation, and apoptosis. Metalloproteinases are classified into three families: Matrix-MPs (MMPs), A-Disintegrin-and-Metalloprotease (ADAMs), and the A-Disintegrin-and-Metalloproteinase-with-Thrombospondin-1-like-Domains (ADAMTS). Previous studies showed that MPs are involved in the development of aortic aneurysms (AA) and, concomitantly, in the onset of chronic kidney disease (CKD). CKD has been, per se, associated with an increased risk for AA. The aim of this review is to examine the pathways that may associate MPs with CKD and AA. Several MMPs, such as MMP-2, -8, -9, and TIMP-1 have been shown to damage the AA wall and to have a toxic effect on renal tubular cells, leading to fibrosis. Similarly, ADAM10 and 17 have been shown to degrade collagen in the AA wall and to worsen kidney function via pro-inflammatory stimuli, the impairment of the Renin-Angiotensin-Aldosterone System, and the degradation of structural proteins. Moreover, MMP-2 and -9 inhibitors reduced aneurysm growth and albuminuria in experimental and human studies. It would be important, in the future, to expand research on MPs from both a prognostic, namely, to refine risk stratification in CKD patients, and a predictive perspective, likely to improve prognosis in response to targeted treatments.
Systematic Review of Nicotine Exposure’s Effects on Neural Stem and Progenitor Cells
Authors: Brooks Arrin C. , Henderson Brandon J.
Published: January 2021

While various modalities of chronic nicotine use have been associated with numerous negative consequences to human health, one possible benefit of nicotine exposure has been uncovered. The discovery of an inverse correlation between smoking and Parkinson’s disease, and later Alzheimer’s disease as well, motivated investigation of nicotine as a neuroprotective agent. Some studies have demonstrated that nicotine elicits improvements in cognitive function. The hippocampus, along with the subventricular zone (SVZ), is a distinct brain region that allow for ongoing postnatal neurogenesis throughout adulthood and plays a major role in certain cognitive behaviors like learning and memory. Therefore, one hypothesis underlying nicotine-induced neuroprotection is possible effects on neural stem cells and neural precursor cells. On the other hand, nicotine withdrawal frequently leads to cognitive impairments, particularly in hippocampal-dependent behaviors, possibly suggesting an impairment of hippocampal neurogenesis with nicotine exposure. This review discusses the current body of evidence on nicotine’s effects on neural stem cells and neural progenitors. Changes in neural stem cell proliferation, survival, intracellular dynamics, and differentiation following acute and chronic nicotine exposure are examined.
Bidding Strategy in Construction Public Procurement: A Contractor’s Perspective
Authors: Hanák Tomáš , Drozdová Adriana , Marović Ivan
Published: January 2021

A contractor’s ability to prepare a competitive bid for a construction tender is crucial for its survival on the market. The bid price estimation strategy should promote the probability of winning a sufficient amount of tenders but, at the same time, ensure the economic stability and development of the company. This paper aims to address this issue in the area of Czech public construction procurement. The opinions, experiences and practices of contractors were collected through a questionnaire survey, and the data were evaluated with the support of statistical methods. This revealed that Czech contractors mostly base their multicriteria bidding strategy on cost-oriented pricing while considering various aspects such as the risks and attractiveness of the tender. The Czech construction market is generally perceived as oriented toward low costs, and with a relatively common occurrence of abnormally low bids. The findings presented in this paper may help contractors improve their current bidding strategies in public construction procurement.
Sex Hormones in Lymphedema
Authors: Morfoisse Florent , Zamora Audrey , Marchaud Emmanuelle , Nougue Manon , Diallo Leila H. , David Florian , Roussel Emilie , Lacazette Eric , Prats Anne-Catherine , Tatin Florence , Garmy-Susini Barbara
Published: January 2021

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return resulting in swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the limb. Whereas it is clearly established that primary lymphedema is sex-linked with an average ratio of one male for three females, the role of female hormones, in particular estrogens, has been poorly explored. In addition, secondary lymphedema in Western countries affects mainly women who developed the pathology after breast cancer and undergo through hormone therapy up to five years after cancer surgery. Although lymphadenectomy is identified as a trigger factor, the effect of co-morbidities associated to lymphedema remains elusive, in particular, estrogen receptor antagonists or aromatase inhibitors. In addition, the role of sex hormones and gender has been poorly investigated in the etiology of the pathology. Therefore, this review aims to recapitulate the effect of sex hormones on the physiology of the lymphatic system and to investigate whetherhormone therapy could promote a lymphatic dysfunction leading to lymphedema.
Induction of CXCL10-Mediated Cell Migration by Different Types of Galectins
Authors: AbuSamra Dina B. , Panjwani Noorjahan , Argüeso Pablo
Published: January 2021

Chemokines are an extended group of chemoattractant cytokines responsible for the recruitment of leukocytes into tissues. Among them, interferon-γ-inducible protein 10 (CXCL10) is abundantly expressed following inflammatory stimuli and participates in the trafficking of monocytes and activated T cells into sites of injury. Here, we report that different members of the galectin family of carbohydrate-binding proteins promote the expression and synthesis of CXCL10 independently of interferon-γ. Interestingly, CXCL10 induction was observed when galectins came in contact with stromal fibroblasts isolated from human cornea but not other cell types such as epithelial, monocytic or endothelial cells. Induction of CXCL10 by the tandem repeat galectin-8 was primarily associated with the chemotactic migration of THP-1 monocytic cells, whereas the prototype galectin-1 promoted the CXCL10-dependent migration of Jurkat T cells. These results highlight the potential importance of the galectin signature in dictating the recruitment of specific leukocyte populations into precise tissue locations.
Inducible Pluripotent Stem Cells as a Potential Cure for Diabetes
Authors: Verhoeff Kevin , Henschke Sarah J. , Marfil-Garza Braulio A. , Dadheech Nidheesh , Shapiro Andrew Mark James
Published: January 2021

Over the last century, diabetes has been treated with subcutaneous insulin, a discovery that enabled patients to forego death from hyperglycemia. Despite novel insulin formulations, patients with diabetes continue to suffer morbidity and mortality with unsustainable costs to the health care system. Continuous glucose monitoring, wearable insulin pumps, and closed-loop artificial pancreas systems represent an advance, but still fail to recreate physiologic euglycemia and are not universally available. Islet cell transplantation has evolved into a successful modality for treating a subset of patients with ‘brittle’ diabetes but is limited by organ donor supply and immunosuppression requirements. A novel approach involves generating autologous or immune-protected islet cells for transplant from inducible pluripotent stem cells to eliminate detrimental immune responses and organ supply limitations. In this review, we briefly discuss novel mechanisms for subcutaneous insulin delivery and define their shortfalls. We describe embryological development and physiology of islets to better understand their role in glycemic control and, finally, discuss cell-based therapies for diabetes and barriers to widespread use. In response to these barriers, we present the promise of stem cell therapy, and review the current gaps requiring solutions to enable widespread use of stem cells as a potential cure for diabetes.
Enhancement of Oxidation Resistance via Chromium Boron Carbide on Diamond Particles
Authors: Zhang Xuliang , Sun Youhong , Meng Qingnan , Wu Jinhao , He Linkai
Published: January 2021

To improve the oxidation resistance of diamond, chromium boron carbide (Cr–B–C) coatings were synthesized through high temperature solid state synthesis and molten salt method on diamond particles in this paper. After holding the raw material at 900 °C for 2 h, the diamond surface was completely and uniformly covered by Cr–B–C coatings. Oxidation resistance of the diamond coated Cr–B–C was determined by the thermogravimetric analysis (TGA). The results revealed that the Cr–B–C coatings held the diamonds for 100%-mass in air atmosphere until 1151 °C, which was much better than the uncoated diamonds (720 °C) and the B4C-coated diamonds (1090 °C). When Cr–B–C-coated diamond was annealed in air, Cr2O3 and B2O3 were formed as oxygen barrier layer to protect diamond from oxidation. The formation of B2O3 with high temperature fluidity was conducive to avoiding Cr2O3 delamination due to volume expansion during oxidation in air. Furthermore, the presence of Cr2O3 provided lasting protection by reducing the evaporation of B2O3. The oxidation products (B2O3 and Cr2O3) prove a complementary functional protection on diamond particles from oxidation.
Analysis for Stroke Etiology in Duplicated/Accessory MCA-Related Cerebral Infarction: Two Case Report and Brief Literature Review
Authors: Tsuyama Kou , Miyamoto Nobukazu , Shindo Atsuhiko , Hira Kenichiro , Ueno Yuji , Yatomi Kenji , Oishi Hidenori , Hattori Nobutaka
Published: January 2021

Duplication and accessory of the middle cerebral artery (MCA) constitute a rare congenital variation. MCA anomalies are found at a lesser frequency than the vascular anomalies of the other major intracranial arteries. Duplicated/accessory MCA was usually noted incidentally with subarachnoid hemorrhage, due to resulted aneurysmal formation. However, duplicated/accessory MCA-related cerebral infarction is rarer. We report two cases of cerebral infarction due to dissection at the entry of the duplicate/accessory MCA. Both cases were similar in dissected site and clinical course, without headache or injury. In 20 previously reported cases and our two cases of duplicated/accessory MCA-related infarction, mean age (55.8 ± 21.2 years) was slightly younger for cerebral infarction, and stroke etiology was mainly embolism. The main etiologies of stroke were embolism and dissection. Considering embolism etiology, proximal site of arterial diameter changing lesion was a common site for embolism, as duplicated/accessory MCA was usually smaller than normal M1 segment. In cerebral dissection cases, the dissected site was similar to our cases. Numerous mechanisms of dissection were considered, but they mainly included dysfunction of the media and endothelium or shearing stress at the entry of duplication. As the detailed mechanisms of cerebral dissection remain unknown, clinicians should include a differential diagnosis for MCA dissection.
A Review of Selected IBD Biomarkers: From Animal Models to Bedside
Authors: Mizoguchi Emiko , Subramaniam Renuka , Okada Toshiyuki , Mizoguchi Atsushi
Published: January 2021

Inflammatory bowel disease (IBD) is a dysregulated inflammatory condition induced by multiple factors. The etiology of IBD is largely unknown, and the disease progression and prognosis are variable and unpredictable with uncontrolled disease behavior. Monitoring the status of chronic colitis closely is challenging for physicians, because the assessment of disease activity and severity require invasive methods. Using laboratory biomarkers may provide a useful alternative to invasive methods in the diagnosis and management of IBD. Furthermore, patients with ulcerative colitis or Crohn’s disease are also at risk of developing cancer. Annual colonoscopies can help lower the risk for developing colorectal cancer. However, laboratory biomarkers may also be helpful as non-invasive indicators in predicting treatment responses, improving prognosis, and predicting possible tumors. This review addresses selected laboratory biomarkers (including ANCA, chitinase 3-like 1, S100A12/RAGE, calprotectin, and TNF/TNFR2), which are identified by utilizing two well-accepted animal models of colitis, dextran sodium sulfate-induced and T cell receptor alpha knockout colitis models. In addition to being useful for monitoring disease severity, these biomarkers are associated with therapeutic strategies. The factors may regulate the initiation and perpetuation of inflammatory factors in the gut.
ELIHKSIR Web Server: Evolutionary Links Inferred for Histidine Kinase Sensors Interacting with Response Regulators
Authors: Sinner Claude , Ziegler Cheyenne , Jung Yun Ho , Jiang Xianli , Morcos Faruck
Published: January 2021

Two-component systems (TCS) are signaling machinery that consist of a histidine kinases (HK) and response regulator (RR). When an environmental change is detected, the HK phosphorylates its cognate response regulator (RR). While cognate interactions were considered orthogonal, experimental evidence shows the prevalence of crosstalk interactions between non-cognate HK–RR pairs. Currently, crosstalk interactions have been demonstrated for TCS proteins in a limited number of organisms. By providing specificity predictions across entire TCS networks for a large variety of organisms, the ELIHKSIR web server assists users in identifying interactions for TCS proteins and their mutants. To generate specificity scores, a global probabilistic model was used to identify interfacial couplings and local fields from sequence information. These couplings and local fields were then used to construct Hamiltonian scores for positions with encoded specificity, resulting in the specificity score. These methods were applied to 6676 organisms available on the ELIHKSIR web server. Due to the ability to mutate proteins and display the resulting network changes, there are nearly endless combinations of TCS networks to analyze using ELIHKSIR. The functionality of ELIHKSIR allows users to perform a variety of TCS network analyses and visualizations to support TCS research efforts.
Reinforcement Learning for Bit-Flipping Decoding of Polar Codes
Authors: Wang Xiumin , He Jinlong , Li Jun , Shan Liang
Published: January 2021

A traditional successive cancellation (SC) decoding algorithm produces error propagation in the decoding process. In order to improve the SC decoding performance, it is important to solve the error propagation. In this paper, we propose a new algorithm combining reinforcement learning and SC flip (SCF) decoding of polar codes, which is called a Q-learning-assisted SCF (QLSCF) decoding algorithm. The proposed QLSCF decoding algorithm uses reinforcement learning technology to select candidate bits for the SC flipping decoding. We establish a reinforcement learning model for selecting candidate bits, and the agent selects candidate bits to decode the information sequence. In our scheme, the decoding delay caused by the metric ordering can be removed during the decoding process. Simulation results demonstrate that the decoding delay of the proposed algorithm is reduced compared with the SCF decoding algorithm, based on critical set without loss of performance.