bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic
Authors: Choi Jihye , Park Youjeong , Kim Hye-Eun , Song Jihyeok , Lee Daeun , Lee Eunhye , Kang Hyeonjin , Lee Jeeho , Park Jihyeon , Lee Ji-Woo , Ye Seongeun , Lee Seul , Ryu Sohee , Kim Yeojeong , Kim Ye-Ri , Kim Yu-Jin , Lee Yuseon
Published: March 2021

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.
The Experience of Apathy in Dementia: A Qualitative Study
Authors: Baber Waqaar , Chang Chern Yi Marybeth , Yates Jennifer , Dening Tom
Published: March 2021

We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers. Twelve participants (6 dyads of 6 people with dementia and their family carers) were recruited from “memory cafes” (meeting groups for people with dementia and their families), social groups, seminars, and patient and public involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data were collected using validated scales for apathy, cognition, anxiety, and depression. The interviews were semi-structured, focusing on the subjective interpretation of apathy and impacts on behaviour, habits, hobbies, relationships, mood, and activities of daily living. Interviews were recorded and transcribed. Transcripts were analysed using interpretative phenomenological analysis (IPA), which generated codes and patterns that were collated into themes. Four major themes were identified, three of which highlighted the challenging aspects of apathy. One described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them. This study is the first to illustrate the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than previously assumed. Apathy and its effects warrant more attention from clinicians, researchers, and others involved in dementia care.
Reply to Comment on Choi, Y.-J., et al. Cellular Phone Use and Risk of Tumors: Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 8079
Authors: Myung Seung-Kwon , Moskowitz Joel M. , Choi Yoon-Jung , Hong Yun-Chul
Published: March 2021

We appreciate Frank de Vocht and Martin Röösli’s interest [...]
A Mixed-Methods Evaluation of CARE (Cancer and Rehabilitation Exercise): A Physical Activity and Health Intervention, Delivered in a Community Football Trust
Authors: Rutherford Zoe , Zwolinsky Stephen , Kime Nicky , Pringle Andy
Published: March 2021

With increasing cancer survivorship has come an increased necessity to support people living with cancer (PLWC) to have a good quality of life including being physically active. Using mixed methods, the current study aimed to use the RE-AIM evaluation framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) to determine how the football community trust delivered CARE (Cancer and Rehabilitation Exercise) intervention was able to increase participants’ physical activity in order to improve their quality of life and regain physiological and psychological function. Quantitative outcome data were collected at baseline, 3 and 6 months using the Cancer Physical Activity Standard Evaluation Framework questionnaire. Semi-structured focus groups (n = 5) captured participants’ (n = 40) lived experience of the reach, effectiveness, adoption, implementation, and maintenance of CARE. Questionnaire data were analysed using repeated measures ANOVAs and qualitative data were thematically analysed. Following diagnosis, CARE was successful in providing participants with a unique and accessible opportunity to become or restart physically activity, by providing a local, socially supportive, and inclusive environment. This resulted in significant increases in physical activity (F(1.58, 23) = 5.98, p = 0.009), quality of life (QoL) (F(2,36) = 13.12, p = 0.000) and significant reductions in fatigue (F(1.57,31) = 11.19, p = 0.000) over 6 months. Participants also reported becoming more active, recovering physical function, regaining independence, and enhanced psychological well-being as a result of attending CARE. Key design features of CARE were also identified across RE-AIM. CARE, a football community trust delivered physical activity intervention was successful in significantly improving participants’ QoL and in regaining the physical and psychological functioning of people living with cancer. Results suggest that maintaining engagement in CARE for 6 months and beyond can support people to maintain these changes. Engaging in robust evaluations such as this can help organizations to successfully secure future funding for their programs.
Multitemporal Analysis of Land Use and Land Cover within an Oil Block in the Ecuadorian Amazon
Authors: Llerena-Montoya Sergio , Velastegui-Montoya Andrés , Zhirzhan-Azanza Bryan , Herrera-Matamoros Viviana , Adami Marcos , de Lima Aline , Moscoso-Silva Francisco , Encalada Luis
Published: March 2021

The Ecuadorian Amazon is considered a biodiverse region, and at the same time contains the largest number of oil blocks and oilfields in the country. Oil exploitation requires the implementation of oil facilities and related infrastructure, such as roads, water, and energy supply, for operation. These large engineering works can alter the dynamics of the Amazonian natural ecosystems. This paper analyzes the land use and land cover (LULC) change and relates spatial patterns within an oil block located in the province of Orellana, Ecuador. The study was processed in two phases, the first corresponding to the collection and classification of LULC classes within the oil block. The second phase concerned the calculation of landscape metrics, with the purpose of quantitatively characterizing each class. This analysis was carried out for the pre-concession, post-concession scenarios of the oil block and the current scenario of the region. The results revealed that the low predominance of forest cover within the study region is not directly associated with the beginning of the Block 47 concession. On the other hand, a significant reduction of the Coca River was evidenced for the 2018 scenario.
Prediction of Potential and Actual Evapotranspiration Fluxes Using Six Meteorological Data-Based Approaches for a Range of Climate and Land Cover Types
Authors: Mobilia Mirka , Longobardi Antonia
Published: March 2021

Evapotranspiration is the major component of the water cycle, so a correct estimate of this variable is fundamental. The purpose of the present research is to assess the monthly scale accuracy of six meteorological data-based models in the prediction of evapotranspiration (ET) losses by comparing the modelled fluxes with the observed ones from eight sites equipped with eddy covariance stations which differ in terms of vegetation and climate type. Three potential ET methods (Penman-Monteith, Priestley-Taylor, and Blaney-Criddle models) and three actual ET models (the Advection-Aridity, the Granger and Gray, and the Antecedent Precipitation Index method) have been proposed. The findings show that the models performances differ from site to site and they depend on the vegetation and climate characteristics. Indeed, they show a wide range of error values ranging from 0.18 to 2.78. It has been not possible to identify a single model able to outperform the others in each biome, but in general, the Advection-Aridity approach seems to be the most accurate, especially when the model calibration in not carried out. It returns very low error values close to 0.38. When the calibration procedure is performed, the most accurate model is the Granger and Gray approach with minimum error of 0.13 but, at the same time, it is the most impacted by this process, and therefore, in a context of data scarcity, it results the less recommended for ET prediction. The performances of the investigated ET approaches have been furthermore tested in case of lack of measured data of soil heat fluxes and net radiation considering using empirical relationships based on meteorological data to derive these variables. Results show that, the use of empirical formulas to derive ET estimates increases the errors up to 200% with the consequent loss of model accuracy.
Assessment of Amyloid Forming Tendency of Peptide Sequences from Amyloid Beta and Tau Proteins Using Force-Field, Semi-Empirical, and Density Functional Theory Calculations
Authors: Muvva Charuvaka , Murugan Natarajan Arul , Subramanian Venkatesan
Published: March 2021

A wide variety of neurodegenerative diseases are characterized by the accumulation of protein aggregates in intraneuronal or extraneuronal brain regions. In Alzheimer’s disease (AD), the extracellular aggregates originate from amyloid-β proteins, while the intracellular aggregates are formed from microtubule-binding tau proteins. The amyloid forming peptide sequences in the amyloid-β peptides and tau proteins are responsible for aggregate formation. Experimental studies have until the date reported many of such amyloid forming peptide sequences in different proteins, however, there is still limited molecular level understanding about their tendency to form aggregates. In this study, we employed umbrella sampling simulations and subsequent electronic structure theory calculations in order to estimate the energy profiles for interconversion of the helix to β-sheet like secondary structures of sequences from amyloid-β protein (KLVFFA) and tau protein (QVEVKSEKLD and VQIVYKPVD). The study also included a poly-alanine sequence as a reference system. The calculated force-field based free energy profiles predicted a flat minimum for monomers of sequences from amyloid and tau proteins corresponding to an α-helix like secondary structure. For the parallel and anti-parallel dimer of KLVFFA, double well potentials were obtained with the minima corresponding to α-helix and β-sheet like secondary structures. A similar double well-like potential has been found for dimeric forms for the sequences from tau fibril. Complementary semi-empirical and density functional theory calculations displayed similar trends, validating the force-field based free energy profiles obtained for these systems.
Mushroom-Derived Medicine? Preclinical Studies Suggest Potential Benefits of Ergothioneine for Cardiometabolic Health
Authors: Lam-Sidun Daniel , Peters Kia M. , Borradaile Nica M.
Published: March 2021

Medicinal use of mushrooms has been documented since ancient times, and in the modern world, mushrooms have a longstanding history of use in Eastern medicine. Recent interest in plant-based diets in Westernized countries has brought increasing attention to the use of mushrooms and mushroom-derived compounds in the prevention and treatment of chronic diseases. Edible mushrooms are the most abundant food sources of the modified amino acid, ergothioneine. This compound has been shown to accumulate in almost all cells and tissues, but preferentially in those exposed to oxidative stress and injury. The demonstrated cytoprotectant effect of ergothioneine has led many to suggest a potential therapeutic role for this compound in chronic conditions that involve ongoing oxidative stress and inflammation, including cardiovascular and metabolic diseases. However, the in vivo effects of ergothioneine and its underlying therapeutic mechanisms in the whole organism are not as clear. Moreover, there are no well-defined, clinical prevention and intervention trials of ergothioneine in chronic disease. This review highlights the cellular and molecular mechanisms of action of ergothioneine and its potential as a Traditional, Complementary and Alternative Medicine for the promotion of cardiometabolic health and the management of the most common manifestations of cardiometabolic disease.
Analysis of the Structure and Biosynthesis of the Lipopolysaccharide Core Oligosaccharide of Pseudomonas syringae pv. tomato DC3000
Authors: Kutschera Alexander , Schombel Ursula , Schwudke Dominik , Ranf Stefanie , Gisch Nicolas
Published: March 2021

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is important for bacterial viability in general and host–pathogen interactions in particular. Negative charges at its core oligosaccharide (core-OS) contribute to membrane integrity through bridging interactions with divalent cations. The molecular structure and synthesis of the core-OS have been resolved in various bacteria including the mammalian pathogen Pseudomonas aeruginosa. A few core-OS structures of plant-associated Pseudomonas strains have been solved to date, but the genetic components of the underlying biosynthesis remained unclear. We conducted a comparative genome analysis of the core-OS gene cluster in Pseudomonas syringae pv. tomato (Pst) DC3000, a widely used model pathogen in plant–microbe interactions, within the P. syringae species complex and to other plant-associated Pseudomonas strains. Our results suggest a genetic and structural conservation of the inner core-OS but variation in outer core-OS composition within the P. syringae species complex. Structural analysis of the core-OS of Pst DC3000 shows an uncommonly high phosphorylation and presence of an O-acetylated sugar. Finally, we combined the results of our genomic survey with available structure information to estimate the core-OS composition of other Pseudomonas species.
The Pharmacology and Therapeutic Utility of Sodium Hydroselenide
Authors: Samra Kavitej , Kuganesan Mathun , Smith William , Kleyman Anna , Tidswell Robert , Arulkumaran Nishkantha , Singer Mervyn , Dyson Alex
Published: March 2021

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe−/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.
CircRNA—Protein Interactions in Muscle Development and Diseases
Authors: Zheng Shuailong , Zhang Xujia , Odame Emmanuel , Xu Xiaoli , Chen Yuan , Ye Jiangfeng , Zhou Helin , Dai Dinghui , Kyei Bismark , Zhan Siyuan , Cao Jiaxue , Guo Jiazhong , Zhong Tao , Wang Linjie , Li Li , Zhang Hongping
Published: March 2021

Circular RNA (circRNA) is a kind of novel endogenous noncoding RNA formed through back-splicing of mRNA precursor. The biogenesis, degradation, nucleus–cytoplasm transport, location, and even translation of circRNA are controlled by RNA-binding proteins (RBPs). Therefore, circRNAs and the chaperoned RBPs play critical roles in biological functions that significantly contribute to normal animal development and disease. In this review, we systematically characterize the possible molecular mechanism of circRNA–protein interactions, summarize the latest research on circRNA–protein interactions in muscle development and myocardial disease, and discuss the future application of circRNA in treating muscle diseases. Finally, we provide several valid prediction methods and experimental verification approaches. Our review reveals the significance of circRNAs and their protein chaperones and provides a reference for further study in this field.
Genetics of Azoospermia
Authors: Cioppi Francesca , Rosta Viktoria , Krausz Csilla
Published: March 2021

Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%). Whole-Exome Sequencing allowed the discovery of an increasing number of monogenic defects of NOA with a current list of 38 candidate genes. These genes are of potential clinical relevance for future gene panel-based screening. We classified these genes according to the associated-testicular histology underlying the NOA phenotype. The validation and the discovery of novel NOA genes will radically improve patient management. Interestingly, approximately 37% of candidate genes are shared in human male and female gonadal failure, implying that genetic counselling should be extended also to female family members of NOA patients.
The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration
Authors: Ziemkiewicz Natalia , Hilliard Genevieve , Pullen Nicholas A. , Garg Koyal
Published: March 2021

Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies.
An Arabidopsis Oxalyl-CoA Decarboxylase, AtOXC, Is Important for Oxalate Catabolism in Plants
Authors: Foster Justin , Cheng Ninghui , Paris Vincent , Wang Lingfei , Wang Jin , Wang Xiaoqiang , Nakata Paul A.
Published: March 2021

Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well-studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, acyl-activating enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. This enzyme has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Since this initial discovery, this enzyme and proposed pathway have been found to be important to other plants and yeast as well. In this study, we identify, in Arabidopsis, an oxalyl-CoA decarboxylase (AtOXC) that is capable of catalyzing the second step in this proposed pathway of oxalate catabolism. This enzyme breaks down oxalyl-CoA, the product of AtAAE3, into formyl-CoA and CO2. AtOXC:GFP localization suggested that this enzyme functions within the cytosol of the cell. An Atoxc knock-down mutant showed a reduction in the ability to degrade oxalate into CO2. This reduction in AtOXC activity resulted in an increase in the accumulation of oxalate and the enzyme substrate, oxalyl-CoA. Size exclusion studies suggest that the enzyme functions as a dimer. Computer modeling of the AtOXC enzyme structure identified amino acids of predicted importance in co-factor binding and catalysis. Overall, these results suggest that AtOXC catalyzes the second step in this alternative pathway of oxalate catabolism.
Secreted Extracellular Vesicle Molecular Cargo as a Novel Liquid Biopsy Diagnostics of Central Nervous System Diseases
Authors: Monteiro-Reis Sara , Carvalho-Maia Carina , Bart Genevieve , Vainio Seppo J. , Pedro Juliana , Silva Eunice R. , Sales Goreti , Henrique Rui , Jerónimo Carmen
Published: March 2021

Secreted extracellular vesicles (EVs) are heterogeneous cell-derived membranous granules which carry a large diversity of molecules and participate in intercellular communication by transferring these molecules to target cells by endocytosis. In the last decade, EVs’ role in several pathological conditions, from etiology to disease progression or therapy evasion, has been consolidated, including in central nervous system (CNS)-related disorders. For this review, we performed a systematic search of original works published, reporting the presence of molecular components expressed in the CNS via EVs, which have been purified from plasma, serum or cerebrospinal fluid. Our aim is to provide a list of molecular EV components that have been identified from both nonpathological conditions and the most common CNS-related disorders. We discuss the methods used to isolate and enrich EVs from specific CNS-cells and the relevance of its components in each disease context.
Chemically and Green Synthesized ZnO Nanoparticles Alter Key Immunological Molecules in Common Carp (Cyprinus carpio) Skin Mucus
Authors: Rashidian Ghasem , Lazado Carlo C. , Mahboub Heba H. , Mohammadi-Aloucheh Ramin , Prokić Marko D. , Nada Hend S. , Faggio Caterina
Published: March 2021

This study was conducted to compare the effects of commercially available (C) and green synthesized (GS) Zinc oxide nanoparticles (ZnO-NPs) on immunological responses of common carp (Cyprinus carpio) skin mucus. GS ZnO-NPs were generated using Thymus pubescent and characterized by UV–vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Fish (n = 150) were randomly allocated into five groups in triplicate and received a waterborne concentration of 0% (control), 25%, and 50% of LC50 96 h of commercially available (C1 and C2) and green synthesized ZnO-NPs (GS1 and GS2) for 21 days. Results from XRD displayed ZnO-NPs with 58 nm in size and UV-vis DRS, EDX, and FT-IR analysis showed that some functional groups from plant extract bonded to the surface of NPs. The SEM images showed that ZnO-NPs have conical morphology. Acute toxicity study showed a higher dose of LC5096h for green synthesized ZnO-NPs (78.9 mg.L−1) compared to the commercial source (59.95 mg.L−1). The highest activity of lysozyme and alternative complement activity (ACH50) were found in control and GS1 groups. A significant decrease in alkaline phosphatase activity (ALP) was found in C1 and C2 groups compared to other treatments. Protease activity (P) was significantly decreased in the C2 group compared to the control and GS groups. Total immunoglobulin (total Ig) content was the highest in the control. In addition, total Ig in the GS1 group was higher than GS2. The exposure to ZnO-NPs lowered total protein content in all experimental groups when compared to control. Present findings revealed lower induced immunosuppressive effects by green synthesized ZnO-NPs on key parameters of fish skin mucus.
Behavioral Alterations and Decreased Number of Parvalbumin-Positive Interneurons in Wistar Rats after Maternal Immune Activation by Lipopolysaccharide: Sex Matters
Authors: Vojtechova Iveta , Maleninska Kristyna , Kutna Viera , Klovrza Ondrej , Tuckova Klara , Petrasek Tomas , Stuchlik Ales
Published: March 2021

Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.
Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats
Authors: Tapia-Bustos Andrea , Lespay-Rebolledo Carolyne , Vío Valentina , Pérez-Lobos Ronald , Casanova-Ortiz Emmanuel , Ezquer Fernando , Herrera-Marschitz Mario , Morales Paola
Published: March 2021

The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 μL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.
Development of Two-Dimensional Nanomaterials Based Electrochemical Biosensors on Enhancing the Analysis of Food Toxicants
Authors: Raja Iruthayapandi Selestin , Vedhanayagam Mohan , Preeth Desingh Raj , Kim Chuntae , Lee Jong Hun , Han Dong Wook
Published: March 2021

In recent times, food safety has become a topic of debate as the foodborne diseases triggered by chemical and biological contaminants affect human health and the food industry’s profits. Though conventional analytical instrumentation-based food sensors are available, the consumers did not appreciate them because of the drawbacks of complexity, greater number of analysis steps, expensive enzymes, and lack of portability. Hence, designing easy-to-use tests for the rapid analysis of food contaminants has become essential in the food industry. Under this context, electrochemical biosensors have received attention among researchers as they bear the advantages of operational simplicity, portability, stability, easy miniaturization, and low cost. Two-dimensional (2D) nanomaterials have a larger surface area to volume compared to other dimensional nanomaterials. Hence, researchers nowadays are inclined to develop 2D nanomaterials-based electrochemical biosensors to significantly improve the sensor’s sensitivity, selectivity, and reproducibility while measuring the food toxicants. In the present review, we compile the contribution of 2D nanomaterials in electrochemical biosensors to test the food toxicants and discuss the future directions in the field. Further, we describe the types of food toxicity, methodologies quantifying food analytes, how the electrochemical food sensor works, and the general biomedical properties of 2D nanomaterials.
Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function
Authors: Lauer Jasmin C. , Selig Mischa , Hart Melanie L. , Kurz Bodo , Rolauffs Bernd
Published: March 2021

Numerous studies have assembled a complex picture, in which extracellular stimuli and intracellular signaling pathways modulate the chondrocyte phenotype. Because many diseases are mechanobiology-related, this review asked to what extent phenotype regulators control chondrocyte function through the cytoskeleton and cytoskeleton-regulating signaling processes. Such information would generate leverage for advanced articular cartilage repair. Serial passaging, pro-inflammatory cytokine signaling (TNF-α, IL-1α, IL-1β, IL-6, and IL-8), growth factors (TGF-α), and osteoarthritis not only induce dedifferentiation but also converge on RhoA/ROCK/Rac1/mDia1/mDia2/Cdc42 to promote actin polymerization/crosslinking for stress fiber (SF) formation. SF formation takes center stage in phenotype control, as both SF formation and SOX9 phosphorylation for COL2 expression are ROCK activity-dependent. Explaining how it is molecularly possible that dedifferentiation induces low COL2 expression but high SF formation, this review theorized that, in chondrocyte SOX9, phosphorylation by ROCK might effectively be sidelined in favor of other SF-promoting ROCK substrates, based on a differential ROCK affinity. In turn, actin depolymerization for redifferentiation would “free-up” ROCK to increase COL2 expression. Moreover, the actin cytoskeleton regulates COL1 expression, modulates COL2/aggrecan fragment generation, and mediates a fibrogenic/catabolic expression profile, highlighting that actin dynamics-regulating processes decisively control the chondrocyte phenotype. This suggests modulating the balance between actin polymerization/depolymerization for therapeutically controlling the chondrocyte phenotype.
Anti-Platelet Properties of Phenolic and Nonpolar Fractions Isolated from Various Organs of Elaeagnus rhamnoides (L.) A. Nelson in Whole Blood
Authors: Skalski Bartosz , Rywaniak Joanna , Szustka Aleksandra , Żuchowski Jerzy , Stochmal Anna , Olas Beata
Published: March 2021

Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) is a shrub growing in coastal areas. Its organs contain a range of bioactive substances including vitamins, fatty acids, various micro and macro elements, as well as phenolic compounds. Numerous studies of sea buckthorn have found it to have anticancer, anti-ulcer, hepatoprotective, antibacterial, and antiviral properties. Some studies suggest that it also affects the hemostasis system. The aim of the study was to determine the effect of six polyphenols rich and triterpenic acids rich fractions (A–F), taken from various organs of sea buckthorn, on the activation of blood platelets using whole blood, and to assess the effect of the tested fractions on platelet proteins: fraction A (polyphenols rich fraction from fruits), fraction B (triterpenic acids rich fraction from fruits), fraction C (polyphenols rich fraction from leaves), fraction D (triterpenic acids rich fraction from leaves), fraction E (polyphenols rich fraction from twigs), and fraction F (triterpenic acids rich fraction from twigs). Hemostasis parameters were determined using flow cytometry and T-TAS (Total Thrombus-formation Analysis System). Additionally, electrophoresis was performed under reducing and non-reducing conditions. Although all tested fractions inhibit platelet activation, the greatest anti-platelet activity was demonstrated by fraction A, which was rich in flavonol glycosides. In addition, none of the tested fractions (A–F) caused any changes in the platelet proteome, and their anti-platelet potential is not dependent on the P2Y12 receptor.
Recent Advances Clarifying the Structure and Function of Plant Apyrases (Nucleoside Triphosphate Diphosphohydrolases)
Authors: Clark Greg , Brown Katherine A. , Tripathy Manas K. , Roux Stanley J.
Published: March 2021

Studies implicating an important role for apyrase (NTPDase) enzymes in plant growth and development began appearing in the literature more than three decades ago. After early studies primarily in potato, Arabidopsis and legumes, especially important discoveries that advanced an understanding of the biochemistry, structure and function of these enzymes have been published in the last half-dozen years, revealing that they carry out key functions in diverse other plants. These recent discoveries about plant apyrases include, among others, novel findings on its crystal structures, its biochemistry, its roles in plant stress responses and its induction of major changes in gene expression when its expression is suppressed or enhanced. This review will describe and discuss these recent advances and the major questions about plant apyrases that remain unanswered.
The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma
Authors: Choi Eugene , Park Sung Jean , Lee Gunhee , Yoon Seung Kew , Lee Minho , Lee Suk Kyeong
Published: March 2021

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.
Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling
Authors: Hritzo Bernadette , Aghdam Saeed Y. , Legesse Betre , Kaur Amandeep , Cao Maohua , Boerma Marjan , Chakraborty Nabarun , Dimitrov George , Gautam Aarti , Hammamieh Rasha , Wilkins William , Tsioplaya Alena , Holmes-Hampton Gregory P. , Moroni Maria
Published: March 2021

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9–2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.
Engineering a Novel Bivalent Oral Vaccine against Enteric Fever
Authors: Soulier Annelise , Prevosto Claudia , Chol Mary , Deban Livija , Cranenburgh Rocky M.
Published: March 2021

Enteric fever is a major global healthcare issue caused largely by Salmonella enterica serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically engineering the attenuated S. Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two S. Paratyphi A immunogenic elements: flagellin H:a and lipopolysaccharide (LPS) O:2. We first replaced the native S. Typhi fliC gene encoding flagellin with the highly homologous fliC gene from S. Paratyphi A using Xer-cise technology. Next, we replaced the S. Typhi rfbE gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O:2 LPS and prevent its conversion to O:9 through tyvelose epimerase activity. The resulting new strain, ZH9PA, incorporated these two genetic changes and exhibited comparable growth kinetics to the parental ZH9 strain. A formulation containing both ZH9 and ZH9PA strains together constitutes a new bivalent vaccine candidate that targets both S. Typhi and S. Paratyphi A antigens to address a major global healthcare gap for enteric fever prophylaxis. This vaccine is now being tested in a Phase I clinical trial (NCT04349553).
Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration
Authors: Padula Stephanie L. , Velayutham Nivedhitha , Yutzey Katherine E.
Published: March 2021

During the postnatal period, mammalian cardiomyocytes undergo numerous maturational changes associated with increased cardiac function and output, including hypertrophic growth, cell cycle exit, sarcomeric protein isoform switching, and mitochondrial maturation. These changes come at the expense of loss of regenerative capacity of the heart, contributing to heart failure after cardiac injury in adults. While most studies focus on the transcriptional regulation of embryonic or adult cardiomyocytes, the transcriptional changes that occur during the postnatal period are relatively unknown. In this review, we focus on the transcriptional regulators responsible for these aspects of cardiomyocyte maturation during the postnatal period in mammals. By specifically highlighting this transitional period, we draw attention to critical processes in cardiomyocyte maturation with potential therapeutic implications in cardiovascular disease.
Sterile Insect Technique in an Integrated Vector Management Program against Tiger Mosquito Aedes albopictus in the Valencia Region (Spain): Operating Procedures and Quality Control Parameters
Authors: Tur Carlos , Almenar David , Benlloch-Navarro Sandra , Argilés-Herrero Rafael , Zacarés Mario , Dalmau Vicente , Pla Ignacio
Published: March 2021

Aedes albopictus and Aedes aegypti are the main vectors of arboviral diseases such as dengue, Zika and chikungunya viruses. About a third of the world population is currently at risk of contracting Aedes-borne epidemics. In recent years, A. albopictus has drastically increased its distribution in many countries. In the absence of efficient mosquito vector control methods, the sterile insect technique (SIT) is presented as a very promising and environment-friendly control tool. The Agriculture Department of the Valencian Region is promoting an ongoing pilot project to evaluate the efficacy of an integrated vector management program (IVM) based on the use of the SIT as the main method of control. The laboratory studies for evaluating the entomological efficacy of SIT through the phased conditional testing process recommended by World Health Organization and the International Atomic Energy Agency (WHO-IAEA) are addressed. This study describes the routine operating procedures and quality control parameters for the medium-scale rearing of sterile male A. albopictus. More than 15 million sterile males have been produced and released in an area of 80 ha between 2018 and 2020. Of the initial L1 larvae, we recovered 17.2% of male pupae after sex sorting to be sterilized and released on the field, while the rest of the pupae remained available to maintain the rearing colony. The residual percentage of females after sex sorting was on average 0.17%. The obtained values in terms of production and quality control as well as the proposed rearing methodology can be useful for designing a medium-scale mosquito-rearing pipeline.
The Temporal Relationships and Associations between Cutaneous Manifestations and Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study
Authors: Hung Yi-Teng , Le Puo-Hsien , Kuo Chia-Jung , Tang Yu-Chuan , Chiou Meng-Jiun , Chiu Cheng-Tang , Kuo Chang-Fu , Huang Yu-Huei
Published: March 2021

The temporal relationships between inflammatory bowel disease (IBD)-associated cutaneous manifestations and IBD remain uncertain, with existing evidence mostly from separate cross-sectional studies. We sought to determine the risks of IBD-related dermatologic diseases before and after the diagnosis of IBD. We identified 2847 cases of IBD and 14,235 matched controls from the Taiwan National Health Insurance Research Database between 2003 and 2014. The risks of cutaneous manifestations before and after the diagnosis of IBD were estimated with multivariable-adjusted analyses. At diagnosis, IBD was associated with atopic dermatitis (odds ratio (OR) = 1.61; 95% confidence interval (CI), 1.14–2.28), erythema nodosum (OR = 7.44; 95%CI, 3.75–14.77), aphthous stomatitis (OR = 2.01; 95%CI, 1.72–2.35), polyarteritis nodosa (OR = 5.67; 95%CI, 2.69–11.98), rosacea (OR = 1.67, 95%CI = 1.19–2.35), and cutaneous T cell lymphoma (OR = 21.27; 95%CI, 2.37–191.00). IBD was associated with the subsequent development of pyoderma gangrenosum (hazard ratio (HR) = 17.79; 95%CI, 6.35–49.86), erythema nodosum (HR = 6.54; 95%CI, 2.83–15.13), polyarteritis nodosa (HR = 2.69; 95%CI, 1.05–6.90), hidradenitis suppurativa (HR = 2.48; 95%CI, 1.03–5.97), psoriasis (HR = 2.19; 95%CI, 1.27–3.79), rosacea (HR = 1.92; 95%CI, 1.39–2.65), and aphthous stomatitis (HR = 1.45; 95%CI, 1.22–1.72). This study clarified the associations and temporal relationships between cutaneous manifestations and IBD, highlighting the need for interdisciplinary care in the patient with specific dermatologic diseases presenting with abdominal symptoms, or the IBD patients with cutaneous lesions.
The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns
Authors: Rebelos Eleni , Honka Miikka-Juhani , Ekblad Laura , Bucci Marco , Hannukainen Jarna C. , Fernandes Silva Lilian , Virtanen Kirsi A. , Nummenmaa Lauri , Nuutila Pirjo
Published: March 2021

The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.