bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Air-Conditioning Systems Contribute to the Spread of SARS/MERS/COVID-19 Infection? Insights from a Rapid Review of the Literature
Authors: Chirico Francesco , Sacco Angelo , Bragazzi Nicola Luigi , Magnavita Nicola
Published: August 2020

The airborne transmission of SARS-CoV-2 is still debated. The aim of this rapid review is to evaluate the COVID-19 risk associated with the presence of air-conditioning systems. Original studies (both observational and experimental researches) written in English and with no limit on time, on the airborne transmission of SARS-CoV, MERS-CoV, and SARS-CoV-2 coronaviruses that were associated with outbreaks, were included. Searches were made on PubMed/MEDLINE, PubMed Central (PMC), Google Scholar databases, and medRxiv. A snowball strategy was adopted to extend the search. Fourteen studies reporting outbreaks of coronavirus infection associated with the air-conditioning systems were included. All studies were carried out in the Far East. In six out the seven studies on SARS, the role of Heating, Ventilation, and Air Conditioning (HVAC) in the outbreak was indirectly proven by the spatial and temporal pattern of cases, or by airflow-dynamics models. In one report on MERS, the contamination of HVAC by viral particles was demonstrated. In four out of the six studies on SARS-CoV-2, the diffusion of viral particles through HVAC was suspected or supported by computer simulation. In conclusion, there is sufficient evidence of the airborne transmission of coronaviruses in previous Asian outbreaks, and this has been taken into account in the guidelines released by organizations and international agencies for controlling the spread of SARS-CoV-2 in indoor environments. However, the technological differences in HVAC systems prevent the generalization of the results on a worldwide basis. The few COVID-19 investigations available do not provide sufficient evidence that the SARS-CoV-2 virus can be transmitted by HVAC systems.
The Impact of Inclusive Talent Development Model on Turnover Intention of New Generation Employees: The Mediation of Work Passion
Authors: Fang Yang-Chun , Chen Jia-Yan , Zhang Xu-Dong , Dai Xin-Xing , Tsai Fu-Sheng
Published: August 2020

The high turnover rate of new generation employees is becoming an increasingly important issue for business and academia. Based on self-determination theory and conservation of resource theory, our study explores the impact of the inclusive talent development model on the turnover intention of new generation employees and the mediating role of work passion. Based on the questionnaire of 290 new generation employees’ data from China, after common method biases and reliability and validity tests, we used SPSS, Mplus and bootstrapping for empirical analysis. The result showed that the inclusive talent development model includes the diversified talent team construction, rational tolerance of employee’s opinions and failures, emphasis on employee’s training, emphasis on fairness and win–win and emphasis on employee’s advantages. The work passion has been divided into harmonious passion and obsessive passion. Among them, rational tolerance of employee’s opinions and failures, emphasis on employee’s training and emphasis on fairness and win–win have a significant positive impact on harmonious passion. Emphasis on fairness and win–win and emphasis on employee’s advantages have negative correlation with obsessive passion. The employee’s harmonious passion is significantly negatively correlated with the turnover intention and the obsessive passion is significantly positively correlated with the turnover intention. In addition, the harmonious passion plays a mediating role between rational tolerance of employee’s opinions and failures, emphasis on employee’s training, emphasis on fairness and win–win and employee’s turnover intention, while the obsessive passion plays a mediating role between emphasis on fairness and win–win and emphasis on employee’s advantages and employee’s turnover intention.
Psychosocial Implications of Supportive Attitudes towards Intimate Partner Violence against Women throughout the Lifecycle
Authors: Sánchez-Prada Andrés , Delgado-Alvarez Carmen , Bosch-Fiol Esperanza , Ferreiro-Basurto Virginia , Ferrer-Perez Victoria A.
Published: August 2020

Supportive attitudes towards intimate partner violence against women (IPVAW) normalize and promote these aggressive behaviors. As a result, more and more research is proposing the identification, analysis and intervention of these attitudes. However, the vast majority of this research focuses on students. The main objective of this paper is to analyze these supportive attitudes throughout the lifecycle. An opportunity sample of 200 Spanish participants, by age and sex fixed quotas, took part in this study. Attitudes were measured using the Inventory of Distorted Thoughts about Women and Violence, the Inventory of Beliefs about Intimate Partner Violence and the Gender Violence Implicit Association Test, a personalized form of Implicit Association Test (IAT). The results show that explicitly measured supportive attitudes towards intimate partner violence against women differ between age groups, adopting a U-shape distribution: lower acceptance among middle-aged-adults and young-adults and higher acceptance among adolescents and older adults. However, when these attitudes were implicitly measured, the IPVAW rejection increased with age, which is a counter-intuitive result and inconsistent with previous theoretical evidence. In summary, these results support an age effect that differs according to the measure of attitudes used and highlight some difficulties related to based-on-reaction-time measures among older people. This suggests the need for further research on the topic, especially among the older population.
The Effects of Exercise on BDNF Levels in Adolescents: A Systematic Review with Meta-Analysis
Authors: Azevedo Kesley Pablo Morais de , de Oliveira Victor Hugo , Medeiros Gidyenne Christine Bandeira Silva de , Mata Ádala Nayana de Sousa , García Daniel Ángel , Martínez Daniel Guillén , Leitão José Carlos , Knackfuss Maria Irany , Piuvezam Grasiela
Published: August 2020

The aim of this study was to analyze the evidence available in the literature about the effects of exercise on brain-derived neurotrophic factor levels in adolescents. The literature searches were conducted in PubMed, Embase, Scopus, ScienceDirect, Web of Science, SportDiscus, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL. Randomized controlled trials and non-randomized controlled trials performed with adolescents (10–19 years) who underwent different exercise programs and who evaluated BDNF levels before and after the intervention were included. We included six studies, four RCTs and two non-RCTs in the systematic review with a total of 407 adolescents. In two randomized trials and one non-RCT, the intervention groups showed significant improvements in BDNF levels compared with the control group. The results presented in the meta-analysis indicate that despite the positive effect in favor of the intervention, there were no significant differences (standardized mean difference 0.28 ng/mL, 95% confidence interval −0.28 to 0.85; p = 0.32, I² = 0%). The results presented in our review indicate that aerobic exercise programs practiced in moderate- or high-intensity are promising strategies to increase BDNF levels in adolescents. However, further studies are required to support this finding.
Predicting Psychological Distress Amid the COVID-19 Pandemic by Machine Learning: Discrimination and Coping Mechanisms of Korean Immigrants in the U.S.
Authors: Choi Shinwoo , Hong Joo Young , Kim Yong Je , Park Hyejoon
Published: August 2020

The current study examined the predictive ability of discrimination-related variables, coping mechanisms, and sociodemographic factors on the psychological distress level of Korean immigrants in the U.S. amid the COVID-19 pandemic. Korean immigrants (both foreign-born and U.S.-born) in the U.S. above the age of 18 were invited to participate in an online survey through purposive sampling. In order to verify the variables predicting the level of psychological distress on the final sample from 42 states (n = 790), the Artificial Neural Network (ANN) analysis, which is able to examine complex non-linear interactions among variables, was conducted. The most critical predicting variables in the neural network were a person’s resilience, experiences of everyday discrimination, and perception that racial discrimination toward Asians has increased in the U.S. since the beginning of the COVID-19 pandemic.
Effects of Six Weeks of High-Intensity Functional Training on Physical Performance in Participants with Different Training Volumes and Frequencies
Authors: Teixeira Rômulo Vasconcelos , Batista Gilmário Ricarte , Mortatti Arnaldo Luis , Dantas Paulo Moreira Silva , Cabral Breno Guilherme de Araújo Tinôco
Published: August 2020

High-intensity functional training (HIFT) is characterized by presenting high volumes and training intensities with constantly varied exercises. The aim of this study was to analyze the internal training load and the effects of high-intensity functional training on physical performance in subjects with different training volumes and frequencies. A total of 31 volunteers involved in high-intensity functional training (14 men and 17 women) were divided according to their training volumes and frequencies (high training-volume and frequency—HTVF; (n = 17) (nine women and eight men; age: 31.0 ± 6.3 years; height: 168.8 ± 8.1 cm, body weight: 73.6 ± 11.9 kg; BMI: 25.96 kg/m2) and moderate training volume and frequency—MTVF; (n = 14) (eight women and six men; age: 26.6 ± 4.7 years; height: 167.2 ± 8.6 cm, body weight: 75.8 ± 18.0 kg; BMI: 27.33 kg/m2)). The internal training load was determined using the session-rating of perceived exertion method. The monotony index (MI) and training strain (TS) were used to determine training variability during the training weeks. Countermovement vertical jump height, 20-m sprinting and handgrip strength were assessed at baseline and after six weeks of training. There was a time effect for MI ((F(5, 145) = 5.942; p = 0.0001)), TS ((F(5, 145) = 5.734; p = 0.0001)), weekly internal training load ((F(4.006, 116.87) = 4.188; p = 0.003)) and mean weekly internal training load ((F(4.006, 116.87) = 4.188; p = 0.003)). There was no increase in performance in either group for countermovement vertical jump height ((F(1,29) = 6.081; p = 0.050)), sprinting ((F(1,29) = 1.014; p = 0.322)), right handgrip strength ((F(1,29) = 2.522; p = 0.123)) or left handgrip strength ((F(1,29) = 2.550; p = 0.121)). The current findings suggest that six weeks of high-intensity functional training was not able to increase performance in either group. Therefore, different volumes and frequencies do not seem to influence the increase in physical performance of HIFT practitioners.
Effectiveness of Lifestyle Interventions for Prevention of Harmful Weight Gain among Adolescents from Ethnic Minorities: A Systematic Review
Authors: Hayba Nematullah , Elkheir Samiha , Hu Jessica , Allman-Farinelli Margaret
Published: August 2020

The escalating obesity among adolescents is of major concern, especially among those from an ethnic minority background. The adolescent period offers a key opportunity for the implementation of positive lifestyle behaviours as children transition to adulthood. The objective of this review was to examine the effectiveness of lifestyle interventions for adolescents and their impact in ethnic and racial minorities for the prevention of overweight and obesity. Seven electronic databases were searched from 2005 until March 2019 for randomized controlled trials of lifestyle programs conducted in this population. The main outcome was change in Body Mass Index (BMI) z-score (kg/m2) or change in BMI and secondary outcomes were changes in physical activity and diet. Thirty studies met the inclusion criteria. Seven studies reported and/or conducted subgroup analysis to determine if ethnic/racial group affected weight change. None demonstrated an overall decrease in BMI z-score. However, six of the seven demonstrated changes in secondary measures such as fruit and vegetable intake and screen time. Results did not differ by ethnic/racial group for primary and secondary outcomes. Overweight and obesity prevention among adolescents from ethnic minorities is an area that needs further research. There is a lack of interventions that include analyses of effectiveness in ethnic minorities.
Quantification of Exposure to Risk Postures in Truck Assembly Operators: Neck, Back, Arms and Wrists
Authors: Zare Mohsen , Bodin Julie , Sagot Jean-Claude , Roquelaure Yves
Published: August 2020

The study assessed the proportion of time in risky postures for the main joints of the upper limbs in a truck assembly plant and explored the association with musculoskeletal symptoms. Fourteen workstations (13 individuals) of a truck assembly plant were selected, and seven sensors were placed on the body segments of the participants. The sensors included tri-axial accelerometers for the arms and back, inclinometers for the neck and electro-goniometry for quantifying flexion/extension of the right and left hands. The proportions of time in moderate awkward postures were high at all workstations. Neck and wrist excessive awkward postures were observed for most workstations. The average values of the 91st percentile for back flexion and right/left arm elevation were 25°, 62°, and 57°, respectively. The 91st and 9th percentile averages for neck flexion/extension were 35.9° and −4.7°, respectively. An insignificant relationship was found between the percentage of time spent in awkward upper limb posture and musculoskeletal symptoms. The findings provide objective and quantitative data about time exposure, variability, and potential risk factors in the real workplace. Quantitative measurements in the field provide objective data of the body postures and movements of tasks that can be helpful in the musculoskeletal disorders (MSDs) prevention program.
Well-Being and Throwing Speed of Women Handball Players Affected by Feedback
Authors: Soto Diego , García-Herrero Juan Antonio , Carcedo Rodrigo J.
Published: August 2020

This research aims at studying the effect of feedback on well-being (vitality, and positive and negative affect), competence valuation, perceived competence, motivation, and performance (throwing speed and accuracy) in a throwing task. Thirty nine expert women handball players, with experience in international handball competitions, participated in this study. They were indiscriminately ascribed to one of three different experimental conditions measuring feedback: (positive, negative, and none). Significant differences in well-being (positive affect) and throwing speed were found among the three feedback groups. More concretely, higher levels of positive affect and throwing speed were found in the negative feedback group in comparison with the other two groups (positive and no-feedback). These results have important implications for athletes’ well-being and performance, and for coaches’ training programs.
Physical Activity Habits and Well-Being among 6-Year-Old Children: The “Improving Umbrian Kids’ Healthy Lifestyle”, an Uncontrolled Pilot Study Project
Authors: Pippi Roberto , Buratta Livia , Germani Alessandro , Fanelli Carmine Giuseppe , Mazzeschi Claudia
Published: August 2020

There is evidence that promoting physical activity programs and decreasing sedentary behavior is a potential strategy for improving health-outcomes, peer relationships and social/emotional well-being in at-risk youth. The World Health Organization recommends enhancing physical education and school-based programs with multi-component and evidence-based assessment methodology. In Umbria (Italy) an uncontrolled pilot study project referred to as “Improving Umbrian kids’ healthy lifestyle” was implemented as a systemic school-based intervention directed at 6-year-old primary school children. The intervention applied a consolidated assessment methodology developed by the C.U.R.I.A.Mo. and Eurobis projects that inserted two hours per week of physical education activity into the school curriculum, structured and supervised by specialists with Exercise and Sport Science degrees, for eight months (from October to June) of the school year. We measured anthropometric values (BMI, waist circumference, waist-to-height ratio index) with objective tools. Moreover, we evaluated physical performance variables (speed, strength, and flexibility) using standard tests. Additionally, self-report measures (measured physical activity during the week, sedentary habits, and psychological well-being) were assessed using validated questionnaires. We observed a significant decrease in waist to height ratio, and improvements in physical performance values and self-report questionnaire measures. Our study suggests that the promotion of physical activity in the school setting is likely to result in physically, mentally, and psycho-socially healthier primary-school-age children.
Maternal Iron Deficiency Programs Offspring Cognition and Its Relationship with Gastrointestinal Microbiota and Metabolites
Authors: Hsieh Hsin-Yi , Chen Yu-Chieh , Hsu Mei-Hsin , Yu Hong-Ren , Su Chung-Hao , Tain You-Lin , Huang Li-Tung , Sheen Jiunn-Ming
Published: August 2020

Iron is an essential micronutrient for the brain development of the fetus. Altered intestinal microbiota might affect behavior and cognition through the so-called microbiota-gut-brain axis. We used a Sprague-Dawley rat model of a maternal low-iron diet to explore the changes in cognition, dorsal hippocampal brain-derived neurotrophic factor (BDNF) and related pathways, gut microbiota, and related metabolites in adult male offspring. We established maternal iron-deficient rats by feeding them a low-iron diet (2.9 mg/kg), while the control rats were fed a standard diet (52.3 mg/kg). We used a Morris water maze test to assess spatial learning and long-term memory. Western blot (WB) assays and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect the BDNF concentration and related signaling pathways. We collected fecal samples for microbiota profiling and measured the concentrations of plasma short-chain fatty acids. The adult male offspring of maternal rats fed low-iron diets before pregnancy, during pregnancy and throughout the lactation period had (1) spatial deficits, (2) a decreased BDNF mRNA expression and protein concentrations, accompanied by a decreased TrkB protein abundance, (3) a decreased plasma acetate concentration, and (4) an enrichment of the Bacteroidaceae genus Bacteroides and Lachnospiraceae genus Marvinbryantia. Maternal iron deficiency leads to an offspring spatial deficit and is associated with alternations in gastrointestinal microbiota and metabolites.
Differences in Thematic Map Reading by Students and Their Geography Teacher
Authors: Beitlova Marketa , Popelka Stanislav , Vozenilek Vit
Published: August 2020

A school world atlas is likely the first systematic cartographic product which students encounter in their lives. However, only a few empirical studies have analysed school atlases in the context of map reading and learning geographical curricula. The present paper describes an eye-tracking study conducted on 30 grammar school students and their geography teacher. The study explored ten tasks using thematic world maps contained in the Czech school world atlas. Three research questions were posed: (i) Are students able to learn using these particular types of maps? (ii) Have the cartographic visualization methods in the school atlas been adequately selected? (iii) Does the teacher read the maps in the same manner as students? The results proved that the students were sufficiently able to learn using thematic maps. The average correctness of their answers exceeded 70%. However, the results highlighted several types of cartographic visualization methods which students found difficult to read. Most of the difficulties arose from map symbols being poorly legible. The most problematic task was estimating the value of the phenomenon from the symbol size legend. Finally, the difference between the students’ and teacher’s manner of reading maps in each task was analysed qualitatively and then quantitatively by applying two different scanpath comparison methods. The study revealed that the geography teacher applied a different method than her students. She avoided looking at the map legend and solved the task using her knowledge.
The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner
Authors: Seifert Anke , Wozniak Justyna , Düsterhöft Stefan , Kasparek Petr , Sedlacek Radislav , Dreschers Stephan , Orlikowsky Thorsten W. , Yildiz Daniela , Ludwig Andreas
Published: August 2020

Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative and -positive bacteria (E. coli and S. aureus, respectively) by human and murine monocytic cell lines or primary phagocytes. Bone marrow-derived macrophages showed enhanced uptake of heat-inactivated and living E. coli when they lacked either ADAM17 or iRhom2 but not upon ADAM10-deficiency. In monocytic THP-1 cells, corresponding short hairpin RNA (shRNA)-mediated knockdown confirmed that ADAM17, but not ADAM10, promoted phagocytosis of E. coli. The augmented bacterial uptake occurred in a cell autonomous manner and was accompanied by increased release of the chemokine CXCL8, less TNFα release and only minimal changes in the surface expression of the receptors TNFR1, TLR6 and CD36. Inhibition experiments indicated that the enhanced bacterial phagocytosis after ADAM17 knockdown was partially dependent on TNFα-activity but not on CXCL8. This novel role of ADAM17 in bacterial uptake needs to be considered in the development of ADAM17 inhibitors as therapeutics.
Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
Authors: Wasel Ola , Freeman Jennifer L.
Published: August 2020

The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system.
Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression
Authors: Wei Jinfen , Hu Meiling , Huang Kaitang , Lin Shudai , Du Hongli
Published: August 2020

The extracellular matrix (ECM) spatiotemporally controls cell fate; however, dysregulation of ECM remodeling can lead to tumorigenesis and cancer development by providing favorable conditions for tumor cells. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the major macromolecules composing ECM. They influence both cell behavior and matrix properties through direct and indirect interactions with various cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes, and glycoproteins within the ECM. The classical features of PGs/GAGs play well-known roles in cancer angiogenesis, proliferation, invasion, and metastasis. Several lines of evidence suggest that PGs/GAGs critically affect broader aspects in cancer initiation and the progression process, including regulation of cell metabolism, serving as a sensor of ECM’s mechanical properties, affecting immune supervision, and participating in therapeutic resistance to various forms of treatment. These functions may be implemented through the characteristics of PGs/GAGs as molecular bridges linking ECM and cells in cell-specific and context-specific manners within the tumor microenvironment (TME). In this review, we intend to present a comprehensive illustration of the ways in which PGs/GAGs participate in and regulate several aspects of tumorigenesis; we put forward a perspective regarding their effects as biomarkers or targets for diagnoses and therapeutic interventions.
Drosophila melanogaster Sperm under Simulated Microgravity and a Hypomagnetic Field: Motility and Cell Respiration
Authors: Ogneva Irina V. , Usik Maria A. , Burtseva Maria V. , Biryukov Nikolay S. , Zhdankina Yuliya S. , Sychev Vladimir N. , Orlov Oleg I.
Published: August 2020

The role of the Earth’s gravitational and magnetic fields in the evolution and maintenance of normal processes of various animal species remains unclear. The aim of this work was to determine the effect of simulated microgravity and hypomagnetic conditions for 1, 3, and 6 h on the sperm motility of the fruit fly Drosophila melanogaster. In addition to the usual diet, the groups were administered oral essential phospholipids at a dosage of 500 mg/kg in medium. The speed of the sperm tails was determined by video recording and analysis of the obtained video files, protein content by western blotting, and cell respiration by polarography. The results indicated an increase in the speed of movement of the sperm tails after 6 h in simulated microgravity. The levels of proteins that form the axoneme of the sperm tail did not change, but cellular respiration was altered. A similar effect occurred with the administration of essential phospholipids. These results may be due to a change in the level of phosphorylation of motor proteins. Exposure to hypomagnetic conditions led to a decrease in motility after 6 h against a background of a decrease in the rate of cellular respiration due to complex I of the respiratory chain. This effect was not observed in the flies that received essential phospholipids. However, after 1 h under hypomagnetic conditions, the rate of cellular respiration also increased due to complex I, including that in the sperm of flies receiving essential phospholipids.
Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice
Authors: Rijal Santosh , Cho Dong Hyu , Park Seon-Ah , Jang Seon Hui , Ábrahám István M. , Han Seong Kyu
Published: August 2020

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.
Ionizing Radiation-Induced Epigenetic Modifications and Their Relevance to Radiation Protection
Authors: Belli Mauro , Tabocchini Maria Antonella
Published: August 2020

The present system of radiation protection assumes that exposure at low doses and/or low dose-rates leads to health risks linearly related to the dose. They are evaluated by a combination of epidemiological data and radiobiological models. The latter imply that radiation induces deleterious effects via genetic mutation caused by DNA damage with a linear dose-dependence. This picture is challenged by the observation of radiation-induced epigenetic effects (changes in gene expression without altering the DNA sequence) and of non-linear responses, such as non-targeted and adaptive responses, that in turn can be controlled by gene expression networks. Here, we review important aspects of the biological response to ionizing radiation in which epigenetic mechanisms are, or could be, involved, focusing on the possible implications to the low dose issue in radiation protection. We examine in particular radiation-induced cancer, non-cancer diseases and transgenerational (hereditary) effects. We conclude that more realistic models of radiation-induced cancer should include epigenetic contribution, particularly in the initiation and progression phases, while the impact on hereditary risk evaluation is expected to be low. Epigenetic effects are also relevant in the dispute about possible “beneficial” effects at low dose and/or low dose-rate exposures, including those given by the natural background radiation.
P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases
Authors: Illes Peter
Published: August 2020

ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population.
Convalescent Immunity to Guinea Pig Cytomegalovirus Induces Limited Cross Strain Protection against Re-Infection but High-Level Protection against Congenital Disease
Authors: Choi K. Yeon , El-Hamdi Nadia S. , McGregor Alistair
Published: August 2020

The guinea pig is the only small animal model for congenital cytomegalovirus (cCMV) but requires guinea pig cytomegalovirus (GPCMV). Current GPCMV research utilizes prototype strain 22122, which limits the translational impact of GPCMV as numerous human CMV strains exist and cCMV is possible in the setting of re-infection. A novel strain of GPCMV (TAMYC) exhibited differences to 22122 in various glycoproteins with GP74 (gO homolog) the most variable (25% difference). Antibody ELISAs for TAMYC-convalescent animals evoked similar immune response to viral glycoprotein complexes (gB, gH/gL, gM/gN, pentamer) and cell-mediated response to pp65 homolog (GP83). Convalescent sera from TAMYC-infected animals neutralized GPCMV infection on fibroblasts but was less effective on epithelial cells. TAMYC-convalescent animals were not protected from dissemination of heterogenous virus challenge (22122). However, in a cCMV protection study, TAMYC-convalescent animals challenged mid-pregnancy (22122) exhibited high-level protection against cCMV compared to seronegative animals with pup transmission reduced from 80% (control) to 12%. Overall, pre-existing immunity in guinea pigs provides limited ability to prevent GPCMV re-infection by a different viral strain but provides a high level of protection against cCMV in heterogenous strain challenge. This level of cross protection against cCMV should be a prerequisite of any CMV vaccine.
Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity
Authors: Sakaguchi Wakako , Kubota Nobuhisa , Shimizu Tomoko , Saruta Juri , Fuchida Shinya , Kawata Akira , Yamamoto Yuko , Sugimoto Masahiro , Yakeishi Mayumi , Tsukinoki Keiichi
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.
Are Myths and Preconceptions Preventing Us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis?
Authors: Shamshina Julia L. , Rogers Robin D.
Published: August 2020

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug’s safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.
Role of CGRP in Neuroimmune Interaction via NF-κB Signaling Genes in Glial Cells of Trigeminal Ganglia
Authors: Afroz Shaista , Arakaki Rieko , Iwasa Takuma , Waskitho Arief , Oshima Masamitsu , Matsuka Yoshizo
Published: August 2020

Activation of the trigeminal system causes the release of various neuropeptides, cytokines, and other immune mediators. Calcitonin gene-related peptide (CGRP), which is a potent algogenic mediator, is expressed in the peripheral sensory neurons of trigeminal ganglion (TG). It affects the inflammatory responses and pain sensitivity by modulating the activity of glial cells. The primary aim of this study was to use array analysis to investigate the effect of CGRP on the glial cells of TG in regulating nuclear factor kappa B (NF-κB) signaling genes and to further check if CGRP in the TG can affect neuron-glia activation in the spinal trigeminal nucleus caudalis. The glial cells of TG were stimulated with CGRP or Minocycline (Min) + CGRP. The effect on various genes involved in NF-κB signaling pathway was analyzed compared to no treatment control condition using a PCR array analysis. CGRP, Min + CGRP or saline was directly injected inside the TG and the effect on gene expression of Egr1, Myd88 and Akt1 and protein expression of cleaved Caspase3 (cleav Casp3) in the TG, and c-Fos and glial fibrillary acidic protein (GFAP) in the spinal section containing trigeminal nucleus caudalis was analyzed. Results showed that CGRP stimulation resulted in the modulation of several genes involved in the interleukin 1 signaling pathway and some genes of the tumor necrosis factor pathway. Minocycline pre-treatment resulted in the modulation of several genes in the glial cells, including anti-inflammatory genes, and neuronal activation markers. A mild increase in cleav Casp3 expression in TG and c-Fos and GFAP in the spinal trigeminal nucleus of CGRP injected animals was observed. These data provide evidence that glial cells can participate in neuroimmune interaction due to CGRP in the TG via NF-κB signaling pathway.
Garlic Substrate Induces Cucumber Growth Development and Decreases Fusarium Wilt through Regulation of Soil Microbial Community Structure and Diversity in Replanted Disturbed Soil
Authors: Ali Ahmad , Ghani Muhammad Imran , Haiyan Ding , Iqbal Muhammad , Cheng Zhihui , Cai Zucong
Published: August 2020

Garlic substrate could influence plant growth through affecting soil microbiome structure. The relationship mechanism between changes in soil microbial communities, disease suppression and plant development, however, remains unclear, particularly in the degraded soil micro-ecological environment. In this study, garlic substrates as a soil amendment were incorporated with different ratios (1:100, 3:100 and 5:100 g/100 g of soil) in a replanted disturbed soil of long-term cucumber monoculture (annual double cropping system in a greenhouse). The results indicated that higher amount of C-amended garlic substrate significantly induced soil suppressiveness (35.9% greater than control (CK) against the foliar disease incidence rate. This inhibitory effect consequently improved the cucumber growth performance and fruit yield to 20% higher than the non-amended soil. Short-term garlic substrate addition modified the soil quality through an increase in soil organic matter (SOM), nutrient availability and enzymatic activities. Illumina MiSeq sequencing analysis revealed that soil bacterial and fungal communities in the garlic amendment were significantly different from the control. Species richness and diversity indices significantly increased under treated soil. The correlation-based heat map analysis suggested that soil OM, nutrient contents and biological activators were the primary drivers reshaping the microbial community structure. Furthermore, garlic substrate inhibited soil-borne pathogen taxa (Fusarium and Nematoda), and their reduced abundances, significantly affecting the crop yield. In addition, the host plant recruited certain plant-beneficial microbes due to substrate addition that could directly contribute to plant–pathogen inhibition and crop biomass production. For example, abundant Acidobacteria, Ascomycota and Glomeromycota taxa were significantly associated with cucumber yield promotion. Firmicutes, Actinobacteria, Bacteroidetes, Basidiomycota and Glomeromycota were the associated microbial taxa that possibly performed as antagonists of Fusarium wilt, with plant pathogen suppression potential in monocropped cucumber-planted soil.
Structure of the Assemblages of Spiders in Mediterranean Pear Orchards and the Effect of Intensity of Spraying
Authors: de Pedro Luis , Ortín-Angulo María Carmen , Miñano Jesús , López-Gallego Elena , Sanchez Juan Antonio
Published: August 2020

Spiders are key predatory arthropods that are negatively affected by spraying pesticides in orchards. The aim of this research was to determine the structure of the community of spiders in pear orchards and the impact of the intensity of spraying. The study was carried out over three years in four pear orchards in southern Spain; two of them were conducted by ourselves with no or low-intensity spraying of insecticides, and two under the criteria of technicians (conventional). Spiders were sampled on pear trees by the beating method. The orchards hosted a rich community of spiders belonging to 13 different families and 51 genera. However, the genera Philodromus, Oxyopes, Cheiracanthium, Icius, and Neoscona accounted for 72% of the captures. Spiders were more abundant and had a higher richness of genera in the low-intensity spraying than in conventional orchards. Philodromidae, Salticidae, and Cheiracanthiidae experienced a significant population reduction in conventional orchards, while Araneidae, Linyphiidae, and Thomisidae were not significantly affected by the intensity of spraying. The wandering hunting mode could explain the negative impact on Philodromidae, Salticidae, and Cheiracanthiidae but does not explain the lack of effect on Oxyopidae and Thomisidae. No significant effect was found on any family of web builders.
Host Ant Change of a Socially Parasitic Butterfly (Phengaris alcon) through Host Nest Take-Over
Authors: Tartally András , Somogyi Anna Ágnes , Révész Tamás , Nash David R.
Published: August 2020

The socially parasitic Alcon blue butterfly (Phengaris alcon) starts its larval stage by feeding on the seeds of gentians, after which it completes development in the nests of suitable Myrmica ant species. The host plant and host ant species can differ at the population level within a region, and local adaptation is common, but some host switches are observed. It has been suggested that one mechanism of change is through the re-adoption of caterpillars by different ant species, either through occupation of abandoned nests or take-over of established nests by competitively superior colonies. To test this question in the lab we introduced relatively strong colonies (50 workers) of alien Myrmica species to the arenas of weaker colonies (two caterpillars with six workers), and to orphaned caterpillars (two caterpillars without ants). We used caterpillars from a xerophylic population of P. alcon, and both local hosts, M. sabuleti and M. scabrinodis, testing the possibility of host switch between these two host ant species during larval development. Most of the caterpillars were successfully readopted by alien ants, and survived well. Our results suggest higher ecological plasticity in host ant usage of this butterfly than generally thought.
Optimal Antithrombotic Treatment of Patients with Atrial Fibrillation Early after an Acute Coronary Syndrome—Triple Therapy, Dual Antithrombotic Therapy with an Anticoagulant… Or, Rather, Temporary Dual Antiplatelet Therapy?
Authors: Limbruno Ugo , De Sensi Francesco , Cresti Alberto , Picchi Andrea , Lena Fabio , De Caterina Raffaele
Published: August 2020

The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y12 inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y12 inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF–ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA2DS2VASc score 2–4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial.
Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients
Authors: Richter Florian , Baratay Annette , Röder Christian , Egberts Jan-Hendrik , Kalthoff Holger , Becker Thomas , Sebens Susanne
Published: August 2020

Hematogenic tumor cell spread is a key event in metastasis. However, the clinical significance of circulating tumor cells (CTC) in the blood and disseminated tumor cells (DTC) in bone marrow is still not fully understood. Here, the presence of DTC and CTC in esophageal cancer (EC) patients and its correlation with clinical parameters was investigated to evaluate the CTC/DTC prognostic value in EC. This study included 77 EC patients with complete surgical tumor resection. CTC and DTC were analyzed in blood and bone marrow using nested CK20 reverse transcription-nested polymerase chain reaction (RT-PCR) and findings were correlated with clinical data. Twenty-seven of 76 patients (36.5%) showed CK20 positivity in the blood, 19 of 61 patients (31.1%) in bone marrow, and 40 (51.9%) of 77 patients were positive in either blood or bone marrow or both. In multivariate analyses, only the DTC status emerged as independent predictor of overall and tumor specific survival. Our study revealed that, while the presence of CTC in blood is not associated with a worse prognosis, DTC detection in the bone marrow is a highly specific and independent prognostic marker in EC patients. Larger cohort studies could unravel how this finding can be translated into improved therapy management in EC.