bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Analysis of AC Dielectric Strength of Natural Ester-Based ZnO Nanofluids
Authors: Duzkaya Hidir , Beroual Abderrahmane
Published: December 2020

Due to environmental concerns and increased energy demand, natural esters are among the alternatives to mineral oils in transformers. This study examines the electrical behavior of natural ester-based ZnO nanofluids at different concentrations in the range of 0.05–0.4 g/L. AC breakdown voltages are measured in a horizontally positioned sphere–sphere electrode system according to IEC 60156 specifications. The measurement data are analyzed using Weibull and normal distribution functions. Breakdown voltages with 1%, 10% and 50% probability are also estimated, these probabilities being of great interest for the design of power electrical components. Experimental results show that AC breakdown voltage increases with the concentration of ZnO nanoparticles, except for the concentration of 0.05 and 0.4 g/L of ZnO. Moreover, breakdown voltages at 1% and 10% probability increase by 22.7% and 13.2% when adding 0.1 g/L ZnO to natural ester, respectively.
Energetic-Environmental-Economic Feasibility and Impact Assessment of Grid-Connected Photovoltaic System in Wastewater Treatment Plant: Case Study
Authors: Andrei Horia , Badea Cristian Andrei , Andrei Paul , Spertino Filippo
Published: December 2020

Wastewater treatment plants and power generation constitute inseparable parts of present society. So the growth of wastewater treatment plants is accompanied by an increase in the energy consumption, and a sustainable development implies the use of renewable energy sources on a large scale in the power generation. A case study of the synergy between wastewater treatment plants and photovoltaic systems, aiming to improve the energetic, environmental and economic impacts, is presented. Based on data acquisition, the energy consumption analysis of wastewater treatment plant reveals that the highest demand is during April, and the lowest is during November. The placement of photovoltaic modules is designed to maximize the use of free space on the technological area of wastewater treatment plant in order to obtain a power output as high as possible. The peak consumption of wastewater treatment plant occurs in April, however the peak production of the photovoltaic is in July, so electrochemical batteries can partly compensate for this mismatch. The impact of the photovoltaic system connectivity on power grid is assessed by means of the matching-index method and the storage battery significantly improves this parameter. Carbon credit and energy payback time are used to assess the environmental impact. The results prove that the photovoltaic system mitigates 12,118 tons of carbon and, respectively, the embedded energy is compensated by production in 8 ½ years. The economic impact of the photovoltaic system is analyzed by the levelized cost of energy, and the results show that the price of energy from the photovoltaic source is below the current market price of energy.
Use of a Pulsed Electric Field to Improve the Biogas Potential of Maize Silage
Authors: Szwarc Dawid , Szwarc Karolina
Published: December 2020

Some types of biomass require great inputs to guarantee high conversion rates to methane. The complex structure of lignocellulose impedes its penetration by cellulolytic enzymes, as a result of which a longer retention time is necessary to increase the availability of nutrients. To use the full biogas potential of lignocellulosic substrates, a substrate pretreatment is necessary before the proper methane fermentation. This article discusses the impact of the pretreatment of maize silage with a pulsed electric field on biogas productivity. The experiment showed a slight decrease in cellulose, hemicellulose and lignin content in the substrate following pretreatment with a pulsed electric field, which resulted in a higher carbohydrate content in the liquid substrate fraction. The highest biogas production output was obtained for the pretreated sample at the retention time of 180 s for 751.97 mL/g volatile solids (VS), which was approximately 14% higher than for the control sample. The methane production rate for the control sample was 401.83 mL CH4/g VS, and for the sample following disintegration it was 465.62 mL CH4/g VS. The study found that pretreatment of maize silage with a pulsed electric field increased the biogas potential.
Effect of Bentonite on the Early Growth Characteristics of Teak Seedlings Planted in Sandy Soil in Northeast Thailand—A Pilot Study
Authors: Kayama Masazumi , Nimpila Suchat , Hongthong Sutjaporn , Yoneda Reiji , Himmapan Woraphun , Noda Iwao
Published: December 2020

The growth of teak (Tectona grandis L. f.) seedlings in sandy soil in northeast Thailand is suppressed by infertility and drought stress. In a preliminary field pot experiment, we confirmed that bentonite was useful for increasing soil water availability. To monitor early growth characteristics of teak seedlings in sandy soil, we curried out an experiment of teak seedlings using bentonite and fertilizer in the field from July 2014 to November 2015. We then compared the growth, biomass, photosynthetic rate, leaf water potential, and concentration of elements in the plant organs among the four treatments. Bentonite increased both soil pH and Ca during the experimental period, and retained P in fertilizer. The dry mass of teak seedlings was markedly increased by concurrent use of bentonite and fertilizer. However, the use of bentonite alone showed little increase of dry mass of teak seedlings. Moreover, application of bentonite was mitigated drought stress in dry season, and photosynthetic rate showed high value by high concentration of chlorophyll. The concentration of K in root of teak seedlings was increased by application of bentonite, and its value showed positive correlation with the relative growth rate of teak seedlings. We concluded that bentonite was useful for the uptake of K and retention of P in fertilizer, as a result, growth of teak seedlings was accelerated.
Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction
Authors: Bai Zhaochen , Zhao Hu , Lin Shaobin , Huang Linhuan , He Zhiming , Wang Huan , Ou Xueling
Published: December 2020

As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.
Insights into the Thermal History of North-Eastern Switzerland—Apatite Fission Track Dating of Deep Drill Core Samples from the Swiss Jura Mountains and the Swiss Molasse Basin
Authors: Villagómez Díaz Diego , Omodeo-Salé Silvia , Ulyanov Alexey , Moscariello Andrea
Published: December 2020

This work presents new apatite fission track LA–ICP–MS (Laser Ablation Inductively Coupled Plasma Mass Spectrometry) data from Mid–Late Paleozoic rocks, which form the substratum of the Swiss Jura mountains (the Tabular Jura and the Jura fold-and-thrust belt) and the northern margin of the Swiss Molasse Basin. Samples were collected from cores of deep boreholes drilled in North Switzerland in the 1980s, which reached the crystalline basement. Our thermochronological data show that the region experienced a multi-cycle history of heating and cooling that we ascribe to burial and exhumation, respectively. Sedimentation in the Swiss Jura Mountains occurred continuously from Early Triassic to Early Cretaceous, leading to the deposition of maximum 2 km of sediments. Subsequently, less than 1 km of Lower Cretaceous and Upper Jurassic sediments were slowly eroded during the Late Cretaceous, plausibly as a consequence of the northward migration of the forebulge of the neo-forming North Alpine Foreland Basin. Following this event, the whole region remained relatively stable throughout the Paleogene. Our data show that the Tabular Jura region resumed exhumation at low rates in early–middle Miocene times (≈20–15 Ma), whereas exhumation in the Jura fold-and-thrust belt probably re-started later, in the late Miocene (≈10–5 Ma). Erosional exhumation likely continues to the present day. Despite sampling limitations, our thermochronological data record discrete periods of slow cooling (rates of about 1°C/My), which might preclude models of elevated cooling (due to intense erosion) in the Jura Mountains during the Miocene. The denudation (≈1 km) of the Tabular Jura region and the Jura fold-and-thrust belt (≈500 m) has provided sediments to the Swiss Molasse Basin since at least 20 Ma. The southward migration of deformation in the Jura mountains suggests that the molasse basin started to uplift and exhume only after 5 Ma, as suggested also by previous authors. The data presented here show that the deformation of the whole region is occurring in an out-of-sequence trend, which is more likely associated with the reactivation of thrust faults beneath the foreland basin. This deformation trend suggests that tectonics is the most determinant factor controlling denudation and exhumation of the region, whereas the recently proposed “climate-induced exhumation” mechanism might play a secondary role.
New Stress Reduction Factor for Evaluating Soil Liquefaction in the Coastal Area of Catania (Italy)
Authors: Grasso Salvatore , Massimino Maria Rossella , Sammito Maria Stella Vanessa
Published: December 2020

In this paper, a study concerning the soil liquefaction potential in the city of Catania is presented. The stress-based liquefaction analysis framework for cohesionless soil includes a function that describes fundamental aspects of dynamic site response, i.e., the shear stress reduction coefficient, rd, which depends on several factors (depth; earthquake and ground motion characteristics; dynamic soil properties). Various relationships of rd are reported in literature because of the importance of assessment of CSR. Herein, new variations of rd with depth have been obtained using different deterministic earthquake scenarios as input motion. The relationships are based on large numbers of site response analyses for different site conditions. The new relationships obtained have been used for the evaluation of the liquefaction potential in the area of the Catania Harbour. The liquefaction resistance has been evaluated by the horizontal stress index (KD) from seismic dilatometer Marchetti tests (SDMTs). Various correlations were developed to estimate the CRR from KD, expressed in form of CRR-KD curves to differentiate between liquefiable and non-liquefiable zones. In this study three different CRR-KD curves have been used.
Low Vision Profile in Jordan: A Vision Rehabilitation Center-Based Study
Authors: Qutishat Yuser , Shublaq Sami , Masoud Maisaa , Alnuman Nasim
Published: December 2020

The aim of this paper is to study the profile of persons with low vision in Jordan based on the clinical records of service users who attended the Vision Rehabilitation Center (VRC) at the German Jordanian University (GJU). A retrospective study was conducted by reviewing the archived data for persons with low vision attending the VRC over the period September 2012 to December 2017. The information collected included age, gender, referral, geographical distribution, chief functional visual problems, and ocular pathology. The records of 725 (28.9 ± 20.3 years old) persons out of 858 persons were analyzed. Almost half (50.6%) of the sample was less than 18 years old. The main cause of the low vision was retinal diseases (53.4%), followed by albinism. Gender and age showed no significant influence on ocular pathology distribution. For the referrals, ophthalmologists (37.8%) were the largest source of referral, followed by institutions for people with disabilities (14.9%). Near tasks were reported as the main functional problems for patients with low vision (74.9%), followed by distance tasks (8.3%). This study sets a precedent for determining the characteristics of persons with low vision in Jordan. Developing an efficient referral system between eye health care professionals and other health caregivers is important to ensure the best multidisciplinary services for low vision.
Architectural, Constructional and Structural Aspects of a Historic School in Greece. The Case of the Elementary School in Arnaia, Chalkidiki
Authors: Pachta Vasiliki , Terzi Vasiliki , Malandri Evangeli
Published: December 2020

Historic school buildings were built during the end of the 19th century and into the beginning of the 20th century, using the traditional and locally available building materials and techniques, and most of them still function as schools. Because of the requirements arising from their constant use, there is an intense interest in their structural and energy integration, while there is limited research on the tangible and intangible values they encompass. In this study, an effort has been made to assess the historical, architectural, constructional and structural aspects of a historic school building located in the town of Arnaia, in the mountainous part of Chalkidiki peninsula, Northern Greece. The study included on-site inspection, architectural overview, determination and mapping of the constructional materials and techniques applied, as well as investigation of the preservation state of the building. Additionally, a structural analysis of the system was performed through a three-dimensional finite element model. All research data was comparatively evaluated, in order to identify the principles governing its physiognomy and structure. The objective of the study was therefore to analyze the significance and technological aspects of this unrecognized part of the common European built heritage that should be further assessed and acknowledged as a heritage asset.
Loneliness, Malnutrition and Change in Subjective Age among Older Adults during COVID-19 Pandemic
Authors: Vitman Schorr Adi , Yehuda Itamar , Tamir Snait
Published: December 2020

Objectives: We examined the effect of loneliness and the role of two mediating factors, depressive symptoms and malnutrition on subjective age among older adults during the 2020 COVID-19 pandemic, and explored how the pandemic is affecting subjective age. Design: A convenience sample of 201 older adults aged 65 and over was interviewed. Using bootstrapping, we tested the strength and significance of the indirect effect of depressive symptoms and malnutrition (mediators) on the relationship between feelings of loneliness and subjective age. Results: The relationship between feelings of loneliness and subjective age during the COVID-19 pandemic was mediated by malnutrition, but not by depressive symptoms. In addition, the participants felt older during the COVID-19 pandemic compared with the preceding period. Conclusions: An association was found among feelings of loneliness, malnutrition, and subjective age. To overcome these feelings in times of crisis like the pandemic, it is essential to develop new communication methods (technologies for managing and addressing the needs of the older population; technologies to encourage social engagement, and technologies for managing and providing remote medical services) for and with older adults that are effective in reducing loneliness, and to promote good nutrition. Possible practical solutions include new social network technologies for reducing loneliness combined with continued reliance on phone communication as an intervention of psychological support to promote a healthy lifestyle and prevent malnutrition.
Promoting Public Engagement during the COVID-19 Crisis: How Effective Is the Wuhan Local Government’s Information Release?
Authors: Yang Yi , Deng Wen , Zhang Yi , Mao Zijun
Published: December 2020

During times of public crises (such as COVID-19), governments must act swiftly to release crisis information effectively and efficiently to the public. This paper provides a general overview of the way that the Wuhan local government use Weibo as a channel to engage with their citizens during the COVID-19 pandemic. Based on the media richness, dialogic loop, and a series of theoretically relevant factors, such as content type, text length, and information source, we try to examine how citizen engage with their local government. By analyzing the data mining samples from Wuhan Release, the official Sina Weibo account of Wuhan’s local government, results show that, despite the unstable situation COVID-19 over the crisis, there exist three stages of a crisis on the whole. Combining the behavior of the government and the public, duration from 31 December 2019 to 19 January 2020 could be seen as the development period, then the outbreak period (30 January 2020 to 28 February 2020), and a grace period (29 February 2020 to19 April 2020). Public attention to different types of information changes over time, but curbing rumors has always been a priority. Media richness features partially influent citizen engagement. Text length is significantly positively associated with citizen engagement through government social media. However, posts containing information sources have a negative impact on citizen engagement.
Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China
Authors: Wang Mengying , Wang Siyue , Wang Xiaowen , Wu Junhui , Wu Yao , Wang Zijing , Wang Jiating , Wu Tao , Hu Yonghua
Published: December 2020

Background: Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene–cIMT interactions’ association with IS risk. Methods: A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records’ review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. Results: We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92–3.20) for IS and 2.75 (2.08–3.64) for LAA (both p trend <0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. Conclusions: Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.
Environmental, Economic and Social Impact Assessment: Study of Bridges in China’s Five Major Economic Regions
Authors: Zhou ZhiWu , Alcalá Julián , Yepes Víctor
Published: December 2020

The construction industry of all countries in the world is facing the issue of sustainable development. How to make effective and accurate decision-making on the three pillars (Environment; Economy; Social influence) is the key factor. This manuscript is based on an accurate evaluation framework and theoretical modelling. Through a comprehensive evaluation of six cable-stayed highway bridges in the entire life cycle of five provinces in China (from cradle to grave), the research shows that life cycle impact assessment (LCIA), life cycle cost assessment (LCCA), and social impact life assessment (SILA) are under the influence of multi-factor change decisions. The manuscript focused on the analysis of the natural environment over 100 years, material replacement, waste recycling, traffic density, casualty costs, community benefits and other key factors. Based on the analysis data, the close connection between high pollution levels and high cost in the maintenance stage was deeply promoted, an innovative comprehensive evaluation discrete mathematical decision-making model was established, and a reasonable interval between gross domestic product (GDP) and sustainable development was determined.
Developing Age-Friendly Cities and Communities: Eleven Case Studies from around the World
Authors: Rémillard-Boilard Samuèle , Buffel Tine , Phillipson Chris
Published: December 2020

Developing age-friendly cities and communities has become a key part of policies aimed at improving the quality of life of older people in urban areas. The World Health Organization has been especially important in driving the ‘age-friendly’ agenda, notably through its Global Network of Age-Friendly Cities and Communities, connecting 1114 (2020 figure) cities and communities worldwide. Despite the expansion and achievements of the Network over the last decade, little is known about the progress made by cities developing this work around the world. This article addresses this research gap by comparing the experience of eleven cities located in eleven countries. Using a multiple case study approach, the study explores the key goals, achievements, and challenges faced by local age-friendly programs and identifies four priorities the age-friendly movement should consider to further its development: (1) changing the perception of older age; (2) involving key actors in age-friendly efforts; (3) responding to the (diverse) needs of older people; and (4) improving the planning and delivery of age-friendly programs. The article concludes by discussing the research and policy implications of these findings for the age-friendly movement.
Oral Health and Autism Spectrum Disorders: A Unique Collaboration between Dentistry and Occupational Therapy
Authors: Como Dominique H. , Stein Duker Leah I. , Polido José C. , Cermak Sharon A.
Published: December 2020

Children with autism spectrum disorders (ASD) are at risk for oral health disparities. With the dramatic rise in ASD prevalence to 1 in 54 children, it is likely that an increasing number of dental practitioners will encounter or be asked to treat children with ASD. This paper reviews explanations related to the increasing prevalence of ASD, provides reasons why children with ASD are at increased risk for poor oral health, and discusses unique interprofessional collaborations between dental practitioners and occupational therapists. Occupational therapists and dentists can work together to plan modifications to the dental environment or adapt dental protocols to reduce some of the barriers encountered by those with ASD, provide desensitization strategies before the clinic visit, or help a child with emotional regulation during clinical treatments.
Iron Oxide Particles Alter Bacterial Uptake and the LPS-Induced Inflammatory Response in Macrophages
Authors: Williams Lewis J. , Tristram Stephen G. , Zosky Graeme R.
Published: December 2020

Exposure to geogenic (earth-derived) particulate matter (PM) is linked to severe bacterial infections in Australian Aboriginal communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of silica and iron oxide on the inflammatory response and bacterial phagocytosis in macrophages. THP-1 and peripheral blood mononuclear cell-derived macrophages were exposed to iron oxide (haematite or magnetite) or silica PM with or without exposure to lipopolysaccharide. Cytotoxicity and inflammation were assessed by LDH assay and ELISA respectively. The uptake of non-typeable Haemophilus influenzae by macrophages was quantified by flow cytometry. Iron oxide increased IL-8 production while silica also induced significant production of IL-1β. Both iron oxide and silica enhanced LPS-induced production of TNF-α, IL-1β, IL-6 and IL-8 in THP-1 cells with most of these responses replicated in PBMCs. While silica had no effect on NTHi phagocytosis, iron oxide significantly impaired this response. These data suggest that geogenic particles, particularly iron oxide PM, cause inflammatory cytokine production in macrophages and impair bacterial phagocytosis. These responses do not appear to be linked. This provides a possible mechanism for the link between exposure to these particles and severe bacterial infection.
Crepis vesicaria L. subsp. taraxacifolia Leaves: Nutritional Profile, Phenolic Composition and Biological Properties
Authors: Pedreiro Sónia , da Ressurreição Sandrine , Lopes Maria , Cruz Maria Teresa , Batista Teresa , Figueirinha Artur , Ramos Fernando
Published: December 2020

Crepis vesicaria subsp. taraxacifolia (Cv) of Asteraceae family is used as food and in traditional medicine. However there are no studies on its nutritional value, phenolic composition and biological activities. In the present work, a nutritional analysis of Cv leaves was performed and its phenolic content and biological properties evaluated. The nutritional profile was achieved by gas chromatography (GC). A 70% ethanolic extract was prepared and characterized by HLPC-PDA-ESI/MSn. The quantification of chicoric acid was determined by HPLC-PDA. Subsequently, it was evaluated its antioxidant activity by DPPH, ABTS and FRAP methods. The anti-inflammatory activity and cellular viability was assessed in Raw 264.7 macrophages. On wet weight basis, carbohydrates were the most abundant macronutrients (9.99%), followed by minerals (2.74%) (mainly K, Ca and Na), protein (1.04%) and lipids (0.69%), with a low energetic contribution (175.19 KJ/100 g). The Cv extract is constituted essentially by phenolic acids as caffeic, ferulic and quinic acid derivatives being the major phenolic constituent chicoric acid (130.5 mg/g extract). The extract exhibited antioxidant activity in DPPH, ABTS and FRAP assays and inhibited the nitric oxide (NO) production induced by LPS (IC50 = 0.428 ± 0.007 mg/mL) without cytotoxicity at all concentrations tested. Conclusions: Given the nutritional and phenolic profile and antioxidant and anti-inflammatory properties, Cv could be a promising useful source of functional food ingredients.
Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
Authors: Pérez-Roque Lucía , Núñez-Gómez Elena , Rodríguez-Barbero Alicia , Bernabéu Carmelo , López-Novoa José M. , Pericacho Miguel
Published: December 2020

Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.
Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis
Authors: Iba Toshiaki , Levy Jerrold H. , Aihara Koichiro , Kadota Katsuhiko , Tanaka Hiroshi , Sato Koichi , Nagaoka Isao
Published: December 2020

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.
BRAF Controls the Effects of Metformin on Neuroblast Cell Divisions in C. elegans
Authors: Qu Zhi , Ji Shaoping , Zheng Shanqing
Published: December 2020

Metformin has demonstrated substantial potential for use in cancer treatments. Liver kinase B (LKB)-AMP-activated protein kinase (AMPK) and mTOR are reported to be the main targets of metformin in relation to its ability to prevent cancer cell proliferation. However, the role of metformin in the control of neoplastic cancer cell growth is possibly independent of LKB-AMPK and mTOR. Using C. elegans as a model, we found that the neuronal Q-cell divisions in L1-arrested worms were suppressed following metformin treatment in AMPK-deficient mutants, suggesting that the mechanism by which metformin suppresses these cell divisions is independent of AMPK. Our results showed that the mTOR pathway indeed played a role in controlling germ cell proliferation, but it was not involved in the neuronal Q-cell divisions occurring in L1-arrested worms. We found that the neuronal Q-cells divisions were held at G1/S cell stage by metformin in vivo. Additionally, we demonstrated that metformin could reduce the phosphorylation activity of BRAF and block the BRAF-MAPK oncogenesis pathway to regulate neuronal Q-cell divisions during L1 arrest. This work discloses a new mechanism by which metformin treatment acts to promote neuronal cancer prevention, and these results will help promote the study of the anticancer mechanisms underlying metformin treatments.
5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology
Authors: Maffei Massimo E.
Published: December 2020

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.
Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration
Authors: Garces Fabian A. , Scortecci Jessica F. , Molday Robert S.
Published: December 2020

ABCA4 is an ATP-binding cassette (ABC) transporter expressed in photoreceptors, where it transports its substrate, N-retinylidene-phosphatidylethanolamine (N-Ret-PE), across outer segment membranes to facilitate the clearance of retinal from photoreceptors. Mutations in ABCA4 cause Stargardt macular degeneration (STGD1), an autosomal recessive disorder characterized by a loss of central vision and the accumulation of bisretinoid compounds. The purpose of this study was to determine the molecular properties of ABCA4 variants harboring disease-causing missense mutations in the transmembrane domains. Thirty-eight variants expressed in culture cells were analyzed for expression, ATPase activities, and substrate binding. On the basis of these properties, the variants were divided into three classes: Class 1 (severe variants) exhibited significantly reduced ABCA4 expression and basal ATPase activity that was not stimulated by its substrate N-Ret-PE; Class 2 (moderate variants) showed a partial reduction in expression and basal ATPase activity that was modestly stimulated by N-Ret-PE; and Class 3 (mild variants) displayed expression and functional properties comparable to normal ABCA4. The p.R653C variant displayed normal expression and basal ATPase activity, but lacked substrate binding and ATPase activation, suggesting that arginine 653 contributes to N-Ret-PE binding. Our classification provides a basis for better understanding genotype–phenotype correlations and evaluating therapeutic treatments for STGD1.
AMP-Activated Protein Kinase: Do We Need Activators or Inhibitors to Treat or Prevent Cancer?
Authors: Russell Fiona M. , Hardie David Grahame
Published: December 2020

AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance. In response to metabolic stress, it acts to redress energy imbalance through promotion of ATP-generating catabolic processes and inhibition of ATP-consuming processes, including cell growth and proliferation. While findings that AMPK was a downstream effector of the tumour suppressor LKB1 indicated that it might act to repress tumourigenesis, more recent evidence suggests that AMPK can either suppress or promote cancer, depending on the context. Prior to tumourigenesis AMPK may indeed restrain aberrant growth, but once a cancer has arisen, AMPK may instead support survival of the cancer cells by adjusting their rate of growth to match their energy supply, as well as promoting genome stability. The two isoforms of the AMPK catalytic subunit may have distinct functions in human cancers, with the AMPK-α1 gene often being amplified, while the AMPK-α2 gene is more often mutated. The prevalence of metabolic disorders, such as obesity and Type 2 diabetes, has led to the development of a wide range of AMPK-activating drugs. While these might be useful as preventative therapeutics in individuals predisposed to cancer, it seems more likely that AMPK inhibitors, whose development has lagged behind that of activators, would be efficacious for the treatment of pre-existing cancers.
Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer’s Disease, Lithium, and Autophagy
Authors: Damri Odeya , Shemesh Nofar , Agam Galila
Published: December 2020

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug’s neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium’s neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug’s inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium’s neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer’s disease (AD) and in patients, discussing the rationale for the drug’s use in the treatment of AD.
Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research
Authors: Maugeri Andrea , Barchitta Martina , Magnano San Lio Roberta , Li Destri Giovanni , Agodi Antonella , Basile Guido
Published: December 2020

Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.
IFNγ Is a Key Link between Obesity and Th1-Mediated AutoImmune Diseases
Authors: Bae Heekyong R. , Choi Myung-Sook , Kim Suntae , Young Howard A. , Gershwin M. Eric , Jeon Seon-Min , Kwon Eun-Young
Published: December 2020

Obesity, a characteristic of metabolic syndrome, is also associated with chronic inflammation and the development of autoimmune diseases. However, the relationship between obesity and autoimmune diseases remains to be investigated in depth. Here, we compared hepatic gene expression profiles among high-fat diet (HFD) mice using the primary biliary cholangitis (PBC) mouse model based on the chronic expression of interferon gamma (IFNγ) (ARE-Del-/- mice). The top differentially expressed genes affected by upstream transcriptional regulators IFNγ, LPS, and TNFα displayed an overlap in HFD and ARE-Del-/- mice, indicating that obesity-induced liver inflammation may be dependent on signaling via IFNγ. The top pathways altered in HFD mice were mostly involved in the innate immune responses, which overlapped with ARE-Del-/- mice. In contrast, T cell-mediated signaling pathways were exclusively altered in ARE-Del-/- mice. We further evaluated the therapeutic effect of luteolin, known as anti-inflammatory flavonoid, in HFD and ARE-Del-/- mice. Luteolin strongly suppressed the MHC I and II antigen presentation pathways, which were highly activated in both HFD and ARE-Del-/- mice. Conversely, luteolin increased metabolic processes of fatty acid oxidation and oxidative phosphorylation in the liver, which were suppressed in ARE-Del-/- mice. Luteolin also strongly induced PPAR signaling, which was downregulated in HFD and ARE-Del-/- mice. Using human GWAS data, we characterized the genetic interaction between significant obesity-related genes and IFNγ signaling and demonstrated that IFNγ is crucial for obesity-mediated inflammatory responses. Collectively, this study improves our mechanistic understanding of the relationship between obesity and autoimmune diseases. Furthermore, it provides new methodological insights into how immune network-based analyses effectively integrate RNA-seq and microarray data.
Insights into the Interaction of LVV-Hemorphin-7 with Angiotensin II Type 1 Receptor
Authors: Ali Amanat , Johnstone Elizabeth K. M. , Baby Bincy , See Heng B. , Song Angela , Rosengren K. Johan , Pfleger Kevin D. G. , Ayoub Mohammed Akli , Vijayan Ranjit
Published: December 2020

Hemorphins are known for their role in the control of blood pressure. Recently, we revealed the positive modulation of the angiotensin II (AngII) type 1 receptor (AT1R) by LVV-hemorphin-7 (LVV-H7) in human embryonic kidney (HEK293) cells. Here, we examined the molecular binding behavior of LVV-H7 on AT1R and its effect on AngII binding using a nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) assay in HEK293FT cells, as well as molecular docking and molecular dynamics (MD) studies. Saturation and real-time kinetics supported the positive effect of LVV-H7 on the binding of AngII. While the competitive antagonist olmesartan competed with AngII binding, LVV-H7 slightly, but significantly, decreased AngII’s kD by 2.6 fold with no effect on its Bmax. Molecular docking and MD simulations indicated that the binding of LVV-H7 in the intracellular region of AT1R allosterically potentiates AngII binding. LVV-H7 targets residues on intracellular loops 2 and 3 of AT1R, which are known binding sites of allosteric modulators in other GPCRs. Our data demonstrate the allosteric effect of LVV-H7 on AngII binding, which is consistent with the positive modulation of AT1R activity and signaling previously reported. This further supports the pharmacological targeting of AT1R by hemorphins, with implications in vascular and renal physiology.
A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease—Do Mice Lie?
Authors: Fisher Michelle A. , Lloyd Megan L.
Published: December 2020

Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model.
Role of Macrophages and RhoA Pathway in Atherosclerosis
Authors: Kloc Malgorzata , Uosef Ahmed , Kubiak Jacek Z. , Ghobrial Rafik Mark
Published: December 2020

The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches.
Compensation Mechanism of the Photosynthetic Apparatus in Arabidopsis thaliana ch1 Mutants
Authors: Wójtowicz Joanna , Jagielski Adam K. , Mostowska Agnieszka , Gieczewska Katarzyna B.
Published: December 2020

The origin of chlorophyll b deficiency is a mutation (ch1) in chlorophyllide a oxygenase (CAO), the enzyme responsible for Chl b synthesis. Regulation of Chl b synthesis is essential for understanding the mechanism of plant acclimation to various conditions. Therefore, the main aim of this study was to find the strategy in plants for compensation of low chlorophyll content by characterizing and comparing the performance and spectral properties of the photosynthetic apparatus related to the lipid and protein composition in four selected Arabidopsis ch1 mutants and two Arabidopsis ecotypes. Mutation in different loci of the CAO gene, viz., NW41, ch1.1, ch1.2 and ch1.3, manifested itself in a distinct chlorina phenotype, pigment and photosynthetic protein composition. Changes in the CAO mRNA levels and chlorophyllide a (Chlide a) content in ecotypes and ch1 mutants indicated their significant role in the adjustment mechanism of the photosynthetic apparatus to low-light conditions. Exposure of mutants with a lower chlorophyll b content to short-term (1LL) and long-term low-light stress (10LL) enabled showing a shift in the structure of the PSI and PSII complexes via spectral analysis and the thylakoid composition studies. We demonstrated that both ecotypes, Col-1 and Ler-0, reacted to high-light (HL) conditions in a way remarkably resembling the response of ch1 mutants to normal (NL) conditions. We also presented possible ways of regulating the conversion of chlorophyll a to b depending on the type of light stress conditions.