bluuebunny/crossref_metadata_2025 huggingface dataset:
From Niche to Market—An Agent-Based Modeling Approach for the Economic Uptake of Electro-Fuels (Power-to-Fuel) in the German Energy System
Authors: Schnuelle Christian , Kisjes Kasper , Stuehrmann Torben , Thier Pablo , Nikolic Igor , von Gleich Arnim , Goessling-Reisemann Stefan
Published: October 2020

The transition process towards renewable energy systems is facing challenges in both fluctuating electricity generation of photovoltaic and wind power as well as socio-economic disruptions. With regard to sector integration, solutions need to be developed, especially for the mobility and the industry sector, because their ad hoc electrification and decarbonization seem to be unfeasible. Power-to-fuel (P2F) technologies may contribute to bridge the gap, as renewable energy can be transferred into hydrogen and hydrocarbon-based synthetic fuels. However, the renewable fuels production is far from economically competitive with conventional fuels. With a newly developed agent-based model, potential developments in the German energy markets were simulated for a horizon of 20 years from 2016 to 2035. The model was constructed through a participatory modeling process with relevant actors and stakeholders in the field. Model findings suggest that adjusted regulatory framework conditions (e.g., exemptions from electricity surtaxes, accurate prices for CO2-certificates, strong start-up subsidies, and drastic emission reduction quotas) are key factors for economically feasible P2F installations and will contribute to its large-scale integration into the German energy system. While plant capacities do not exceed 0.042 GW in a business-as-usual scenarios, the above-mentioned adjustments lead to plant capacities of at least 3.25 GW in 2035 with concurrent reduction in product prices.
Comparative Analysis of System Performance and Thermal Comfort for an Integrated System with PVT and GSHP Considering Two Load Systems: Convective Heating and Radiant Floor Heating
Authors: Bae Sangmu , Nam Yujin , Choi Joon-Ho
Published: October 2020

The zero-energy building (ZEB) concept has a high potential for securing energy savings in the building sector. To achieve ZEB, various active systems, including renewable systems such as photovoltaic, solar heating, and geothermal systems, have been developed. However, the existing systems are costly or not optimized. To overcome these issues, the authors previously developed an integrated tri-generation system. In this research, the previously developed system was comprehensively analyzed considering the indoor thermal comfort and energy efficiency to develop a design and operation method for the integrated system. Two different heating systems (convective heating and radiant floor heating) were employed in the tri-generation system, and their system performance, predicted mean vote (PMV), and predicted percentage of dissatisfied (PPD) were compared using simulations. The results showed that the heating coefficient of power of the radiant floor heating system was 18.8% higher than that of the convective heating system. Moreover, the radiant floor heating system (Case 4) met the PMV and PPD standards during all the heating periods. Overall, radiant floor heating was found to be more efficient than convective heating. The results confirm that radiant floor heating is more suitable than convective heating considering the indoor thermal comfort of occupants.
Monuments Unveiled: Genetic Characterization of Large Old Chestnut (Castanea sativa Mill.) Trees Using Comparative Nuclear and Chloroplast DNA Analysis
Authors: Mattioni Claudia , Ranzino Liliana , Cherubini Marcello , Leonardi Luca , La Mantia Tommaso , Castellana Simone , Villani Fiorella , Simeone Marco Cosimo
Published: October 2020

Large old trees are extraordinary organisms. They not only represent a historical, landscape and environmental heritage of inestimable value, but they also witness a long history of environmental changes and human interventions, and constitute an as yet poorly known reserve of genetic variability which can be considered a great resource for management programs of forest species. This is the first genetic study on Italian, large, old chestnut trees (Castanea sativa Mill.). Ninety-nine trees were surveyed and analysed. For each tree, more than one sample from canopy and root suckers was collected to test for the genetic integrity of the individuals. All samples were genotyped using nine nuclear microsatellite markers (nSSRs) and 106 unique genetic profiles were identified. A Bayesian analysis performed with the software STRUCTURE revealed the occurrence of two main gene pools and unveiled the genetic relationships existing among the genotyped individuals, and with the natural chestnut populations living in proximity. A phylogeographic structure of the plastid diversity was also obtained by the use of DNA sequence variation at two marker regions, revealing different origins and probable connections of the old trees with different glacial refugia. Our results contribute to an improved evaluation of the European chestnut genetic resources and provide useful insights into the species’ history and domestication in Italy. The importance of carefully targeted conservation strategies for these invaluable organisms is reaffirmed.
Techno-Economic Analysis of Bioethanol Plant By-Product Valorization: Exploring Market Opportunities with Protein-Rich Fungal Biomass Production
Authors: Bulkan Gülru , Ferreira Jorge A. , Rajendran Karthik , Taherzadeh Mohammad J.
Published: October 2020

The feasibility of dry-grind bioethanol plants is extremely dependent on selling prices of ethanol and by-products, known as Dried distillers grains with solubles (DDGS), and sold as animal feed. Increasing the amount and quality of the by-products can widen potential feed and food markets and improve the process economy and robustness to price fluctuations of ethanol and grain. In this study, the techno-economic analysis of a bioethanol plant was investigated. Integration of edible filamentous fungi into the process leading to the conversion of sidestreams into ethanol and protein-rich fungal biomass for food and feed applications was considered, and its impact was investigated. Sensitivity analysis considered variations on process capacity, on the price of grain and ethanol, and on the price of fungal biomass considering its use for various animal feed (e.g., pig and fish) and human food markets. Selling the fungal biomass in the human food market resulted in 5.56 times higher NPV (net present value) than the base case bioethanol plant after 20 years. Integration of a low-performing strain towards ethanol, followed by the usage of the fungal biomass in the food sector, was found to be the most resistant scenario to the low ethanol selling price and increasing grain price. This study showed that the competitiveness of ethanol plants in the fuel market could be reinforced while meeting the increasing demand for protein sources.
Real-Time Monitoring of Volatile Compounds Losses in the Oven during Baking and Toasting of Gluten-Free Bread Doughs: A PTR-MS Evidence
Authors: Pico Joana , Khomenko Iuliia , Capozzi Vittorio , Navarini Luciano , Biasioli Franco
Published: October 2020

Losses of volatile compounds during baking are expected due to their evaporation at the high temperatures of the oven, which can lead to a decrease in the aroma intensity of the final product, which is crucial for gluten-free breads that are known for their weak aroma. Volatiles from fermentation and lipids oxidation are transferred from crumb to crust, and they flow out to the air together with Maillard and caramelisation compounds from the crust. In this study, the release to the oven of volatile compounds from five gluten-free breads (quinoa, teff and rice flours, and corn and wheat starches) and wheat bread during baking and toasting was measured in real-time using proton transfer reaction-time of flight-mass spectrometry (PTR-ToF-MS). Baking showed different volatile release patterns that are described by bell-shaped curves, plateaus and exponential growths. Flour-based breads had the higher overall volatile release during baking, but also high ratios in the final bread, while starch-based breads showed high pyrazine releases due to moisture losses. Meanwhile, toasting promoted the release of volatile compounds from the bread matrix, but also the additional generation of volatiles from Maillard reaction and caramelisation. Interestingly, gluten-free breads presented higher losses of volatiles during baking than wheat bread, which could partially explain their weaker aroma.
The Knowledge, Attitude and Practices of the Caregivers about Oral Health Care, at Centers for Intellectually Disabled, in Southern Region of Saudi Arabia
Authors: Abullais Shahabe Saquib , Al-Shahrani Falah Mohammed Falah , Al-Gafel Khalaf Mohammed Saeed , Saeed Al-Harthi Abdulrahman , Al-Mathami Shouq Abdulrahman , Bhavikatti Shaeesta Khaleelahmed , Khan Abdul Ahad Ghaffar
Published: October 2020

Oral health is perhaps the most neglected aspect of healthcare for persons living in rehabilitation centers, compared to the general population. The caregivers play a vital role in administering daily oral care to residents in rehabilitation centers: The aim of the present questionnaire-based study was to evaluate the caregivers’ knowledge, attitude and practices towards oral healthcare at centers for the intellectually disabled in the Southern region of Saudi Arabia (SA). The present study was designed as a cross-sectional one-point time survey. The samples were selected by using a non-probability convenience sampling method. The self-administered closed-ended questionnaire comprised of 22 items divided into four sections, which was designed to elicit the demographic information, awareness of oral care, attitude towards oral health and practice of the oral healthcare regime among the participants. Of the164 participants, 53.0% and 47.0% were male and female, respectively. Most of the participants—54.9%—were between 30–39 years of age. Participants were almost equally distributed between educational groups, and about 87% had more than 2 years of experience. A brief overview showed a fair level of knowledge and attitude among 61.6% and 58.5% of respondents, respectively. Participants with an education level above that of high school showed good knowledge and attitude scores (p < 0.05), whereas females showed better attitude scores compared to the males (p < 0.05). Respondents mentioned the difficulties they faced while treating the subjects. The special healthcare workers generally had acceptable oral health knowledge and practices. Caregivers who had lower education levels should be advised for training programs that addressed the importance of oral health services.
Globalization, Work, and Health: A Nordic Perspective
Authors: Torp Steffen , Reiersen Jon
Published: October 2020

The Nordic countries are among the world’s leading countries in international rankings on prosperity, productivity, social equity, trust, and health. Such positive results may be linked to how these countries have organized their working life. The aim of this article is to describe core elements of the Nordic working life model (emphasizing Norway) and discuss how globalization may challenge the model, and thereby influence public health. Based on an extensive review of relevant research, we show that the Nordic working life model with a coordinated wage bargaining system between well-organized employers and employees results in productive enterprises, small wage differences, good working environments, and a high level of well-being. Global trends of liberalization of working life, increased labor migration, the platform economy, reduced unionization, and more precarious work challenge the Nordic working life model and its reliance on standard working contracts. Such a trend may result in increased inequity, reduced generalized trust, and poorer public health. Politicians and other stakeholders in the Nordic countries should cope appropriately with globalization and technological changes so that the Nordic countries will uphold their well-organized working life and good societal achievements.
Spatiotemporal Big Data for PM2.5 Exposure and Health Risk Assessment during COVID-19
Authors: He Hongbin , Shen Yonglin , Jiang Changmin , Li Tianqi , Guo Mingqiang , Yao Ling
Published: October 2020

The coronavirus disease 2019 (COVID-19) first identified at the end of 2019, significantly impacts the regional environment and human health. This study assesses PM2.5 exposure and health risk during COVID-19, and its driving factors have been analyzed using spatiotemporal big data, including Tencent location-based services (LBS) data, place of interest (POI), and PM2.5 site monitoring data. Specifically, the empirical orthogonal function (EOF) is utilized to analyze the spatiotemporal variation of PM2.5 concentration firstly. Then, population exposure and health risks of PM2.5 during the COVID-19 epidemic have been assessed based on LBS data. To further understand the driving factors of PM2.5 pollution, the relationship between PM2.5 concentration and POI data has been quantitatively analyzed using geographically weighted regression (GWR). The results show the time series coefficients of monthly PM2.5 concentrations distributed with a U-shape, i.e., with a decrease followed by an increase from January to December. In terms of spatial distribution, the PM2.5 concentration shows a noteworthy decline over the Central and North China. The LBS-based population density distribution indicates that the health risk of PM2.5 in the west is significantly lower than that in the Middle East. Urban gross domestic product (GDP) and urban green area are negatively correlated with PM2.5; while, road area, urban taxis, urban buses, and urban factories are positive. Among them, the number of urban factories contributes the most to PM2.5 pollution. In terms of reducing the health risks and PM2.5 pollution, several pointed suggestions to improve the status has been proposed.
Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects
Authors: Crauciuc George Andrei , Iancu Mihaela , Olah Peter , Tripon Florin , Anciuc Mădălina , Gozar Liliana , Togănel Rodica , Bănescu Claudia
Published: October 2020

This study aimed to investigate possible associations of the susceptibility to congenital heart defects (CHDs) with AXIN1 rs1805105, rs12921862 and rs370681 gene variants and haplotypes, and AXIN2 rs2240308 gene variant. Significant associations were identified for AXIN1 rs370681 and AXIN2 rs2240308 variants. AXIN1 rs370681 variant was significantly associated with decreased odds of CHDs (adjusted OR varying from 0.13 to 0.28 in codominant, dominant and recessive gene models), while the AXIN2 rs2240308 variant was associated with increased odds of CHD in the dominant model. The haplotype-based generalized linear model regression of AXIN1 rs1805105, rs12921862 and rs370681 variants revealed that C-C-C and C-C-T haplotypes significantly increased the risk of CHDs (p < 0.05). No significant second order epistatic interactions were found between investigated variants (AXIN1 rs1805105, rs12921862, rs370681, and AXIN2 rs2240308). Our conclusion is that AXIN1 rs1805105, rs12921862, and rs370681 (C-C-C and C-C-T) haplotypes and AXIN2 rs2240308 contribute to CHDs susceptibility.
Relationship between Firefighter Physical Fitness and Special Ability Performance: Predictive Research Based on Machine Learning Algorithms
Authors: Xu Datao , Song Yang , Meng Yao , István Bíró , Gu Yaodong
Published: October 2020

Firefighters require a high level of physical fitness to meet the demands of their job. The correlations and contributions of individual physical health parameters to the tasks of firefighting would enable firefighters to focus on the effects of specific physical conditions during their physical training programs. Therefore, the purpose of the present study was to identify the relationships between various physical health parameters (weight, maximum oxygen uptake, body fat percentage, upper body muscular power and lower body muscular power) and performance on simulated firefighting ability tasks, which included a set of seven tasks (rope climb, run 200 m round trip with load, 60 m carrying a ladder, climb stairs with load, evacuation of 400 m with supplies, run 5 km with an air respirator, run 100 m with the water hose). Through use of a partial least-squares regression (PLSR) algorithm to analyze the linear correlation, we revealed the change in various training performances of specific ability tests with physical fitness parameters. The present study demonstrated significant relationships among physical health parameters and performance on simulated firefighting ability tasks, which also represent that those parameters contributed significantly to the model’s predictive power and were suitable predictors of the simulated firefighting tasks score.
Citation Network Analysis of the Novel Coronavirus Disease 2019 (COVID-19)
Authors: Martinez-Perez Clara , Alvarez-Peregrina Cristina , Villa-Collar Cesar , Sánchez-Tena Miguel Ángel
Published: October 2020

Background: The first outbreaks of the new coronavirus disease, named COVID-19, occurred at the end of December 2019. This disease spread quickly around the world, with the United States, Brazil and Mexico being the countries the most severely affected. This study aims to analyze the relationship between different publications and their authors through citation networks, as well as to identify the research areas and determine which publication has been the most cited. Methods: The search for publications was carried out through the Web of Science database using terms such as “COVID-19” and “SARS-CoV-2” for the period between January and July 2020. The Citation Network Explorer software was used for publication analysis. Results: A total of 14,335 publications were found with 42,374 citations generated in the network, with June being the month with the largest number of publications. The most cited publication was “Clinical Characteristics of Coronavirus Disease 2019 in China” by Guan et al., published in April 2020. Nine groups comprising different research areas in this field, including clinical course, psychology, treatment and epidemiology, were found using the clustering functionality. Conclusions: The citation network offers an objective and comprehensive analysis of the main papers on COVID-19 and SARS-CoV-2.
A 3D Geodatabase for Urban Underground Infrastructures: Implementation and Application to Groundwater Management in Milan Metropolitan Area
Authors: Sartirana Davide , Rotiroti Marco , Zanotti Chiara , Bonomi Tullia , Fumagalli Letizia , De Amicis Mattia
Published: October 2020

The recent rapid increase in urbanization has led to the inclusion of underground spaces in urban planning policies. Among the main subsurface resources, a strong interaction between underground infrastructures and groundwater has emerged in many urban areas in the last few decades. Thus, listing the underground infrastructures is necessary to structure an urban conceptual model for groundwater management needs. Starting from a municipal cartography (Open Data), thus making the procedure replicable, a GIS methodology was proposed to gather all the underground infrastructures into an updatable 3D geodatabase (GDB) for the metropolitan city of Milan (Northern Italy). The underground volumes occupied by three categories of infrastructures were included in the GDB: (a) private car parks, (b) public car parks and (c) subway lines and stations. The application of the GDB allowed estimating the volumes lying below groundwater table in four periods, detected as groundwater minimums or maximums from the piezometric trend reconstructions. Due to groundwater rising or local hydrogeological conditions, the shallowest, non-waterproofed underground infrastructures were flooded in some periods considered. This was evaluated in a specific pilot area and qualitatively confirmed by local press and photographic documentation reviews. The methodology emerged as efficient for urban planning, particularly for urban conceptual models and groundwater management plans definition.
Articulated Trajectory Mapping for Reviewing Walking Tours
Authors: Sasaki Iori , Arikawa Masatoshi , Takahashi Akinori
Published: October 2020

This paper addresses how to enrich a map-based representation for reviewing walking tours with the features of trajectory mapping and tracing animation. Generally, a trajectory generated by raw GPS data can often be difficult to browse through on a map. To resolve this issue, we first illustrated tangled trajectory lines, inaccurate indoor positioning, and unstable trajectory lines as problems encountered when mapping raw trajectory data. Then, we proposed a new framework that focuses on GPS horizontal accuracy to locate indoor location points and find stopping points on an accelerometer. We also applied a conventional line simplification algorithm to make the trajectory cleaner and then integrated the extracted points with the clean trajectory line. Furthermore, our experiments with some actual logs of walking tours demonstrated that articulated trajectory mapping, which comprises simplification and characterization methods, sufficiently reliable and effective for better reviewing experiences. The paper contributes to the research on cleaning up map-based displays and tracing animations of raw trajectory GPS data by using not only location data but also sensor data that smartphones can collect.
The Effect of Allopregnanolone on Enzymatic Activity of the DNA Base Excision Repair Pathway in the Sheep Hippocampus and Amygdala under Natural and Stressful Conditions
Authors: Misztal Tomasz , Kowalczyk Paweł , Młotkowska Patrycja , Marciniak Elżbieta
Published: October 2020

The neurosteroid allopregnanolone (AL) has many beneficial functions in the brain. This study tested the hypothesis that AL administered for three days into the third brain ventricle would affect the enzymatic activity of the DNA base excision repair (BER) pathway in the hippocampal CA1 and CA3 fields and the central amygdala in luteal-phase sheep under both natural and stressful conditions. Acute stressful stimuli, including isolation and partial movement restriction, were used on the last day of infusion. The results showed that stressful stimuli increased N-methylpurine DNA glycosylase (MPG), thymine DNA glycosylase (TDG), 8-oxoguanine glycosylase (OGG1), and AP-endonuclease 1 (APE1) mRNA expression, as well as repair activities for 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC), and 8-oxoguanine (8-oxoG) compared to controls. The stimulated events were lower in stressed and AL-treated sheep compared to sheep that were only stressed (except MPG mRNA expression in the CA1 and amygdala, as well as TDG mRNA expression in the CA1). AL alone reduced mRNA expression of all DNA repair enzymes (except TDG in the amygdala) relative to controls and other groups. DNA repair activities varied depending on the tissue—AL alone stimulated the excision of εA in the amygdala, εC in the CA3 and amygdala, and 8-oxoG in all tissues studied compared to controls. However, the excision efficiency of lesioned bases in the AL group was lower than in the stressed and stressed and AL-treated groups, with the exception of εA in the amygdala. In conclusion, the presented modulating effect of AL on the synthesis of BER pathway enzymes and their repair capacity, both under natural and stressful conditions, indicates another functional role of this neurosteroid in brain structures.
Recycling the Purpose of Old Drugs to Treat Ovarian Cancer
Authors: Nunes Mariana , Henriques Abreu Miguel , Bartosch Carla , Ricardo Sara
Published: October 2020

The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment.
Structural and Functional Brain Abnormalities in Mouse Models of Lafora Disease
Authors: Burgos Daniel , Cussó Lorena , Sánchez-Elexpuru Gentzane , Calle Daniel , Perpinyà Max , Desco Manuel , Serratosa José , Sánchez Marina
Published: October 2020

Mutations in the EPM2A and EPM2B genes, encoding laforin and malin proteins respectively, are responsible for Lafora disease, a fatal form of progressive myoclonus epilepsy with autosomal recessive inheritance. Neuroimaging studies of patients with Lafora disease have shown different degrees of brain atrophy, decreased glucose brain uptake and alterations on different brain metabolites mainly in the frontal cortex, basal ganglia and cerebellum. Mice deficient for laforin and malin present many features similar to those observed in patients, including cognitive, motor, histological and epileptic hallmarks. We describe the neuroimaging features found in two mouse models of Lafora disease. We found altered volumetric values in the cerebral cortex, hippocampus, basal ganglia and cerebellum using magnetic resonance imaging (MRI). Positron emission tomography (PET) of the cerebral cortex, hippocampus and cerebellum of Epm2a−/− mice revealed abnormal glucose uptake, although no alterations in Epm2b−/− mice were observed. Magnetic resonance spectroscopy (MRS) revealed significant changes in the concentration of several brain metabolites, including N-acetylaspartate (NAA), in agreement with previously described findings in patients. These data may provide new insights into disease mechanisms that may be of value for developing new biomarkers for diagnosis, prevention and treatment of Lafora disease using animal models.
Fasting Drives Nrf2-Related Antioxidant Response in Skeletal Muscle
Authors: Lettieri-Barbato Daniele , Minopoli Giuseppina , Caggiano Rocco , Izzo Rossella , Santillo Mariarosaria , Aquilano Katia , Faraonio Raffaella
Published: October 2020

A common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles. Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress. Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle. The nuclear factor erythroid 2-related factor 2 (Nrf2) controls adaptive responses and remains the major regulator of quenching mechanisms underlying different types of stress. Here, we demonstrate a positive role of fasting as a protective mechanism against oxidative stress in skeletal muscle. In particular, by using in vivo and in vitro models of fasting, we found that typical Nrf2-dependent genes, including those controlling iron (e.g., Ho-1) and glutathione (GSH) metabolism (e.g., Gcl, Gsr) are induced along with increased levels of the glutathione peroxidase 4 (Gpx4), a GSH-dependent antioxidant enzyme. These events are associated with a significant reduction in malondialdehyde, a well-known by-product of lipid peroxidation. Our results suggest that fasting could be a valuable approach to boost the adaptive anti-oxidant responses in skeletal muscle.
Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivatives
Authors: Ogloblina Anna M. , Iaccarino Nunzia , Capasso Domenica , Di Gaetano Sonia , Garzarella Emanuele U. , Dolinnaya Nina G. , Yakubovskaya Marianna G. , Pagano Bruno , Amato Jussara , Randazzo Antonio
Published: October 2020

Certain G-quadruplex forming guanine-rich oligonucleotides (GROs), including AS1411, are endowed with cancer-selective antiproliferative activity. They are known to bind to nucleolin protein, resulting in the inhibition of nucleolin-mediated phenomena. However, multiple nucleolin-independent biological effects of GROs have also been reported, allowing them to be considered promising candidates for multi-targeted cancer therapy. Herein, with the aim of optimizing AS1411 structural features to find GROs with improved anticancer properties, we have studied a small library of AS1411 derivatives differing in the sequence length and base composition. The AS1411 derivatives were characterized by using circular dichroism and nuclear magnetic resonance spectroscopies and then investigated for their enzymatic resistance in serum and nuclear extract, as well as for their ability to bind nucleolin, inhibit topoisomerase I, and affect the viability of MCF-7 human breast adenocarcinoma cells. All derivatives showed higher thermal stability and inhibitory effect against topoisomerase I than AS1411. In addition, most of them showed an improved antiproliferative activity on MCF-7 cells compared to AS1411 despite a weaker binding to nucleolin. Our results support the hypothesis that the antiproliferative properties of GROs are due to multi-targeted effects.
Lymph Node Stromal Cells: Mapmakers of T Cell Immunity
Authors: Harlé Guillaume , Kowalski Camille , Garnier Laure , Hugues Stéphanie
Published: October 2020

Stromal cells (SCs) are strategically positioned in both lymphoid and nonlymphoid organs to provide a scaffold and orchestrate immunity by modulating immune cell maturation, migration and activation. Recent characterizations of SCs have expanded our understanding of their heterogeneity and suggested a functional specialization of distinct SC subsets, further modulated by the microenvironment. Lymph node SCs (LNSCs) have been shown to be particularly important in maintaining immune homeostasis and T cell tolerance. Under inflammation situations, such as viral infections or tumor development, SCs undergo profound changes in their numbers and phenotype and play important roles in contributing to either the activation or the control of T cell immunity. In this review, we highlight the role of SCs located in LNs in shaping peripheral T cell responses in different immune contexts, such as autoimmunity, viral and cancer immunity.
Identification, Characterization and Synthesis of Walterospermin, a Sperm Motility Activator from the Egyptian Black Snake Walterinnesia aegyptia Venom
Authors: Abd El-Aziz Tarek Mohamed , Jaquillard Lucie , Bourgoin-Voillard Sandrine , Martinez Guillaume , Triquigneaux Mathilde , Zoukimian Claude , Combemale Stéphanie , Hograindleur Jean-Pascal , Al Khoury Sawsan , Escoffier Jessica , Michelland Sylvie , Bulet Philippe , Beroud Rémy , Seve Michel , Arnoult Christophe , De Waard Michel
Published: October 2020

Animal venoms are small natural mixtures highly enriched in bioactive components. They are known to target at least two important pharmacological classes of cell surface receptors: ion channels and G protein coupled receptors. Since sperm cells express a wide variety of ion channels and membrane receptors, required for the control of cell motility and acrosome reaction, two functions that are defective in infertility issues, animal venoms should contain interesting compounds capable of modulating these two essential physiological functions. Herein, we screened for bioactive compounds from the venom of the Egyptian black snake Walterinnesia aegyptia (Wa) that possess the property to activate sperm motility in vitro from male mice OF1. Using RP-HPLC and cation exchange chromatography, we identified a new toxin of 6389.89 Da (termed walterospermin) that activates sperm motility. Walterospermin was de novo sequenced using a combination of matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF MS/MS) and liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF MS/MS) following reduction, alkylation, and enzymatic proteolytic digestion with trypsin, chymotrypsin or V8 protease. The peptide is 57 amino acid residues long and contains three disulfide bridges and was found to be identical to the previously cloned Wa Kunitz-type protease inhibitor II (Wa Kln-II) sequence. Moreover, it has strong homology with several other hitherto cloned Elapidae and Viperidae snake toxins suggesting that it belongs to a family of compounds able to regulate sperm function. The synthetic peptide shows promising activation of sperm motility from a variety of species, including humans. Its fluorescently-labelled analog predominantly marks the flagellum, a localization in agreement with a receptor that controls motility function.
Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
Authors: Kecskés Angéla , Pohóczky Krisztina , Kecskés Miklós , Varga Zoltán V. , Kormos Viktória , Szőke Éva , Henn-Mike Nóra , Fehér Máté , Kun József , Gyenesei Attila , Renner Éva , Palkovits Miklós , Ferdinandy Péter , Ábrahám István M. , Gaszner Balázs , Helyes Zsuzsanna
Published: October 2020

Somatostatin is an important mood and pain-regulating neuropeptide, which exerts analgesic, anti-inflammatory, and antidepressant effects via its Gi protein-coupled receptor subtype 4 (SST4) without endocrine actions. SST4 is suggested to be a unique novel drug target for chronic neuropathic pain, and depression, as a common comorbidity. However, its neuronal expression and cellular mechanism are poorly understood. Therefore, our goals were (i) to elucidate the expression pattern of Sstr4/SSTR4 mRNA, (ii) to characterize neurochemically, and (iii) electrophysiologically the Sstr4/SSTR4-expressing neuronal populations in the mouse and human brains. Here, we describe SST4 expression pattern in the nuclei of the mouse nociceptive and anti-nociceptive pathways as well as in human brain regions, and provide neurochemical and electrophysiological characterization of the SST4-expressing neurons. Intense or moderate SST4 expression was demonstrated predominantly in glutamatergic neurons in the major components of the pain matrix mostly also involved in mood regulation. The SST4 agonist J-2156 significantly decreased the firing rate of layer V pyramidal neurons by augmenting the depolarization-activated, non-inactivating K+ current (M-current) leading to remarkable inhibition. These are the first translational results explaining the mechanisms of action of SST4 agonists as novel analgesic and antidepressant candidates.
Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity
Authors: Cho Hyun-Woong , Lee Sanghoon , Min Kyung-Jin , Hong Jin Hwa , Song Jae Yun , Lee Jae Kwan , Lee Nak Woo , Kim Tak
Published: October 2020

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient’s age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.
Rational Design of Aptamer-Tagged tRNAs
Authors: Mukai Takahito
Published: October 2020

Reprogramming of the genetic code system is limited by the difficulty in creating new tRNA structures. Here, I developed translationally active tRNA variants tagged with a small hairpin RNA aptamer, using Escherichia coli reporter assay systems. As the tRNA chassis for engineering, I employed amber suppressor variants of allo-tRNAs having the 9/3 composition of the 12-base pair amino-acid acceptor branch as well as a long variable arm (V-arm). Although their V-arm is a strong binding site for seryl-tRNA synthetase (SerRS), insertion of a bulge nucleotide in the V-arm stem region prevented allo-tRNA molecules from being charged by SerRS with serine. The SerRS-rejecting allo-tRNA chassis were engineered to have another amino-acid identity of either alanine, tyrosine, or histidine. The tip of the V-arms was replaced with diverse hairpin RNA aptamers, which were recognized by their cognate proteins expressed in E. coli. A high-affinity interaction led to the sequestration of allo-tRNA molecules, while a moderate-affinity aptamer moiety recruited histidyl-tRNA synthetase variants fused with the cognate protein domain. The new design principle for tRNA-aptamer fusions will enhance radical and dynamic manipulation of the genetic code.
The Role of Zinc in Male Fertility
Authors: Allouche-Fitoussi Deborah , Breitbart Haim
Published: October 2020

Several studies proposed the importance of zinc ion in male fertility. Here, we describe the properties, roles and cellular mechanisms of action of Zn2+ in spermatozoa, focusing on its involvement in sperm motility, capacitation and acrosomal exocytosis, three functions that are crucial for successful fertilization. The impact of zinc supplementation on assisted fertilization techniques is also described. The impact of zinc on sperm motility has been investigated in many vertebrate and invertebrate species. It has been reported that Zn2+ in human seminal plasma decreases sperm motility and that Zn2+ removal enhances motility. Reduction in the intracellular concentration of Zn2+ during epididymal transit allows the development of progressive motility and the subsequent hyper activated motility during sperm capacitation. Extracellular Zn2+ affects intracellular signaling pathways through its interaction with the Zn2+ sensing receptor (ZnR), also named GPR39. This receptor was found in the sperm tail and the acrosome, suggesting the possible involvement of Zn2+ in sperm motility and acrosomal exocytosis. Our studies showed that Zn2+ stimulates bovine sperm acrosomal exocytosis, as well as human sperm hyper-activated motility, were both mediated by GPR39. Zn2+ binds and activates GPR39, which activates the trans-membrane-adenylyl-cyclase (tmAC) to catalyze cAMP production. The NHE (Na+/H+-exchanger) is activated by cAMP, leading in increased pHi and activation of the sperm-specific Ca2+ channel CatSper, resulting in an increase in [Ca2+]i, which, together with HCO3−, activates the soluble adenylyl-cyclase (sAC). The increase in [cAMP]i activates protein kinase A (PKA), followed by activation of the Src-epidermal growth factor receptor-Pphospholipase C (Src-EGFR-PLC) cascade, resulting in inositol-triphosphate (IP3) production, which mobilizes Ca2+ from the acrosome, causing a further increase in [Ca2+]i and the development of hyper-activated motility. PKA also activates phospholipase D1 (PLD1), leading to F-actin formation during capacitation. Prior to the acrosomal exocytosis, PLC induces phosphadidylinositol-4,5-bisphosphate (PIP2) hydrolysis, leading to the release of the actin-severing protein gelsolin to the cytosol, which is activated by Ca2+, resulting in F-actin breakdown and the occurrence of acrosomal exocytosis.
Factors Affecting Decision-Making Processes in Virtual Teams in the UAE
Authors: Davidaviciene Vida , Majzoub Khaled Al , Meidute-Kavaliauskiene Ieva
Published: October 2020

Organizational reliance on virtual teams (VTs) is increasing tremendously due to the significant benefits they offer, such as efficiently reaching objectives and increasing organizational performance. However, VTs face a lot of challenges that, if overlooked, will prevent them from yielding the required benefits. One of the major issues that hinders the effectiveness of VTs is the decision-making process. There is a lack of scientific research that attempts to understand the factors affecting decision making processes in VTs. Studies in this area have only been done in the United States and Europe. However, such research has not been conducted in the Middle East, where specific scientific solutions are still required to improve the performance of VTs. Therefore, this study is conducted in the Middle East, namely in the United Arab Emirates, to gain scientific knowledge on this region’s specificity. An online questionnaire (Google forms) was used to obtain the necessary data. Hypotheses were developed to test the influence of ICT (Information and communications technologies), language, information sharing, and trust on the decision-making processes, and the effect of decision making on team performance. Structural equational model (SEM) methodology was used to test our proposed model. The results showed that factors such as trust, ICT, and information sharing have a direct effect on decision-making processes, while language has no effect on decision making, and decision-making processes have a direct effect on the performance of the VTs.
Populations and Host/Non-Host Plants of Spittlebugs Nymphs in Olive Orchards from Northeastern Portugal
Authors: Villa María , Rodrigues Isabel , Baptista Paula , Fereres Alberto , Pereira José Alberto
Published: October 2020

The Aphrophoridae family contains important vectors of Xylella fastidiosa, a serious bacterial plant disease. In olive orchards, nymphs usually feed on the ground-cover vegetation. However, detailed information about their populations and host/non-host plants in some regions threatened by Xylella, such as the northeast of Portugal, is very limited. The goal of our work was to identify the vector species, nymphal development period, and their host and non-host herbaceous plants in olive orchards from northeastern Portugal. Ground-cover plant species hosting or not hosting nymphs were identified during the spring of 2017 to 2019 in olive orchards. Nymphal development period, nymph aggregation, and nymph’s preferred feeding height of the ground-cover plants were recorded. The most abundant Aphrophoridae species was Philaenus spumarius followed by Neophilaenus sp. Nymphs developed from April to early May and showed a low number of individuals per foam (generally between one and three). They preferred the middle part of the plants. Philaenus spumarius feeds preferentially on Asteraceae and Fabaceae, and Neophilaenus sp. on Poaceae. Some abundant plants, such as Bromus diandrus, Astragalus pelecinus, Chrysanthemum segetum, Trifolium spp., Caryophyllaceae, and Brassicaceae, were barely colonized by Aphrophoridae nymphs. This knowledge is essential for the selection of the species composition of ground-cover vegetation to minimize the presence of vectors of X. fastidiosa in olive groves.
Accuracy of 3-Dimensionally Printed Full-Arch Dental Models: A Systematic Review
Authors: Etemad-Shahidi Yasaman , Qallandar Omel Baneen , Evenden Jessica , Alifui-Segbaya Frank , Ahmed Khaled Elsayed
Published: October 2020

The use of additive manufacturing in dentistry has exponentially increased with dental model construction being the most common use of the technology. Henceforth, identifying the accuracy of additively manufactured dental models is critical. The objective of this study was to systematically review the literature and evaluate the accuracy of full-arch dental models manufactured using different 3D printing technologies. Seven databases were searched, and 2209 articles initially identified of which twenty-eight studies fulfilling the inclusion criteria were analysed. A meta-analysis was not possible due to unclear reporting and heterogeneity of studies. Stereolithography (SLA) was the most investigated technology, followed by digital light processing (DLP). Accuracy of 3D printed models varied widely between <100 to >500 μm with the majority of models deemed of clinically acceptable accuracy. The smallest (3.3 μm) and largest (579 μm) mean errors were produced by SLA printers. For DLP, majority of investigated printers (n = 6/8) produced models with <100 μm accuracy. Manufacturing parameters, including layer thickness, base design, postprocessing and storage, significantly influenced the model’s accuracy. Majority of studies supported the use of 3D printed dental models. Nonetheless, models deemed clinically acceptable for orthodontic purposes may not necessarily be acceptable for the prosthodontic workflow or applications requiring high accuracy.
Belching in Gastroesophageal Reflux Disease: Literature Review
Authors: Sawada Akinari , Fujiwara Yasuhiro , Sifrim Daniel
Published: October 2020

Belching is a common phenomenon. However, it becomes bothersome if excessive. Impedance–pH monitoring can classify the belching into two types: gastric belching and supragastric belching (SGB). The former is a physiological mechanism to vent swallowed air from the stomach, whereas the latter is a behavioral disorder. Gastroesophageal reflux disease (GERD) is the most relevant condition in both types of belching. Recent findings have raised awareness that excessive SGB possibly sheds light on the pathogenesis of a part of proton pump inhibitor (PPI) refractoriness in GERD. SGB could cause typical reflux symptoms such as heartburn, regurgitation or chest pain in two ways: SGB-induced gastroesophageal reflux or SGB-induced esophageal distension. In PPI-refractory GERD, it is important to detect hidden SGB as a cause of reflux symptoms since SGB requires psychological treatment instead of high dose PPIs or pain modulators. In the case of PPI-refractory GERD with excessive SGB, recent studies imply that the combination of a psychological approach and conventional treatment can improve treatment outcome.