bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicles in Heart Disease: Excitement for the Future?
Authors: Danielson Kirsty M. , Das Saumya
Published: September 2020

Extracellular vesicles (EV), including exosomes, microvesicles and apoptotic bodies, are released from numerous cell types and are involved in intercellular communication, physiological functions and the pathology of disease. They have been shown to carry and transfer a wide range of cargo including proteins, lipids and nucleic acids. The role of EVs in cardiac physiology and heart disease is an emerging field that has produced intriguing findings in recent years. This review will outline what is currently known about EVs in the cardiovascular system, including cellular origins, functional roles and utility as biomarkers and potential therapeutics.
Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-Cell Communication
Authors: Campanella Claudia , Bavisotto Celeste Caruso , Gammazza Antonella Marino , Nikolic Dragana , Rappa Francesca , David Sabrina , Cappello Francesco , Bucchieri Fabio , Fais Stefano
Published: September 2020

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.
Results of vitamin and mineral complexes’ use during pregnancy (literature review)
Authors: Kuznetsova I. V.
Published: September 2020

The purpose of this review was to study the effect of the intake of vitamin and mineral complexes (VMC) by pregnant women on obstetric and perinatal outcomes. To carry out the analysis, a search was carried out in foreign and domestic publications in the international citation system PubMed, published over the past 15 years. The results of the analysis showed that the use of VMC within 3 months before conception and during pregnancy reduces the risks of intrauterine abnormalities and improves the prognosis of postnatal development of offspring. In addition, taking VMC during gestation reduces the incidence of iron deficiency anemia in pregnant women, intrahepatic cholestasis of pregnant women, preeclampsia, macrosomia, low birth weight, premature birth and postpartum hemorrhage. The use of multicomponent VMC has advantages over taking only folic acid and iron. Conclusion. Taking an VMC during pregnancy can significantly reduce the risk of adverse obstetric and perinatal outcomes. The use of complex drugs is especially important at the stage of preconception and early pregnancy, but it is advisable to continue until the end of pregnancy and lactation.
Experience of using time-lapse microscopy in IVF and ICSI programs
Authors: Saraeva N. V. , Spiridonova N. V. , Tugushev M. T. , Shurygina O. V. , Sinitsyna A. I.
Published: September 2020

In order to increase the pregnancy rate in the assisted reproductive technology, the selection of one embryo with the highest implantation potential it is very important. Time-lapse microscopy (TLM) is a tool for selecting quality embryos for transfer. This study aimed to assess the benefits of single-embryo transfer of autologous oocytes performed on day 5 of embryo incubation in a TLM-equipped system in IVF and ICSI programs. Single-embryo transfer following incubation in a TLM-equipped incubator was performed in 282 patients, who formed the main group; the control group consisted of 461 patients undergoing single-embryo transfer following a traditional culture and embryo selection procedure. We assessed the quality of transferred embryos, the rates of clinical pregnancy and delivery. The groups did not differ in the ratio of IVF and ICSI cycles, average age, and infertility factor. The proportion of excellent quality embryos for transfer was 77.0% in the main group and 65.1% in the control group (p = 0.001). In the subgroup with receiving eight and less oocytes we noted the tendency of receiving more quality embryos in the main group (р = 0.052). In the subgroup of nine and more oocytes the quality of the transferred embryos did not differ between two groups. The clinical pregnancy rate was 60.2% in the main group and 52.9% in the control group (p = 0.057). The delivery rate was 45.0% in the main group and 39.9% in the control group (p > 0.050).
ANALISIS KOHESI dan KOHEREN PADA WACANA CERPEN KEUTAMAAN SEDEKAH KARYA HABIBURRAHMAN EL SHIRAY
Authors: Setya Nugraha Alfian , Safira Alfaza
Published: September 2020

this study will analyze cohesion and coherence in short stories entitled the primacy of alms the work of  Habiburrahman El Shirazy to find out the use of chesion and coherence in the short stor. In this case cohesion and coherence are one of the important compenents in the formation of a dicourse or text. This study will discuss lexical cohesion and gramaical cohesion and coherent. This research hopes that better writing can be useful for the reader. With that reader can take the mandate conveyed by the author. The menthod of qualitative description is seen in terms of words, phrase sentences or paragraphs. The technique used is to read and take notes.
ANALISIS KOHESI DAN KOHORENSI WACANA BERITA MAHASISWA ITS JADI JAWARA DI RUMANIA DALAM DETIKNEWS
Authors: Khoifatu Amalia Shofiani Arisni , Puspa Wiyanti Belia
Published: September 2020

This journal aims to explain the results of cohesion and cohesion analysis in the ITS Student news discourse to be the Champion in Romania on the May 14, 2019 edition of Deiknews. This study uses descriptive methods describing the results of the analysis found in this study. This research is a type of qualitative research because the results of the research are descriptive and tend to be analysis. The techniques used for data collection are the techniques of listening and note taking techniques. The results of this study are (1) the use of cohesion, (2) the use of cohesion. Cohesion is the integration between the parts that are characterized by the use of language elements. Cohesion is divided into two parts, lexical cohesion and grammatical cohesion. Grammatical cohesion includes conjunction, reference, release, substitution. Lexical cohesion includes antonyms, synonyms, repetitions, metonymy, and hypomini. Whereas, cohorence is the relationship between elements that are one with the other elements so that it has an integrated meaning. The most common combination in discourse is cohesion, namely grammatical cohesion. Grammatical cohesion is reference and conjunction. Therefore, the news discourse does not pay attention in terms of language and only prioritizes the actuality of the content of the news.
ANALISIS WACANA KRITIS: MATA NAJWA ON STAGE KEDIRI “MELIHAT INDONESIA
Authors: Prihatin Yulianah , Farida Deviana
Published: September 2020

Kediri's Talk Show Mata Najwa On Stage, on March 24th 2019 the theme was "Seeing Indonesia". Mata Najwa discusses the small human struggle to become a big person in the country. Because the event was held in Kediri, commonly called the City of Santri, the speakers invited by Najwa Shihab were Indonesian dignitaries from santri. Critical Discourse Analysis is always interesting to study. The researcher will use the Van Dijk analysis model. The results of this discussion are (1) Macro structure contained in the discourse, which is to know Indonesia from boarding schools, how a santri or a small process to become a great person in this country. (2) Superstructure, the opening section opens with an appearance from Nidji's band grub, the introduction opens with a narrative from Najwa Shihab entitled "Seeing Indonesia", then the discussion is displayed video old photo document from JATIM Governor Khofifah Indar Parawansa, MENPORA Imam Nahrowi, Gus Nadzir a students who are permanent lecturers at the University of Australia, and A. Fuadi, the author of the novel Negeri 5 Menara, discussed the challenges faced by Indonesia which included Corruption, Differences, and Reactive attitudes. The closing ceremony ended with messages for the young people from Narasumer. (3) Microstructure, namely the semantic analysis of the questions asked by Najwa Shihab to the speakers
PENGGUNAAN KALIMAT IMPERATIF PADA PRODUK KECANTIKAN UNILEVER
Authors: Kristiana Dian
Published: September 2020

About problem which is assessed deep observational it is subject to be know how imperatif's sentence purpose commands on unilever's beauty product and how imperatif's sentence purpose prohibition on unilever's beauty product. This research intent to describe how imperatif's sentence purpose commands and prohibition purpose on Unilever's beauty product. Observational method that  is utilized  in this research is kualitatif's descriptive method. It becomes research basic because in this research researcher describes imperatif's sentence commands and imperatif's sentence prohibition. Result observationaling to point out that imperatif's sentence purpose on Unilever's beauty product there are many utilize imperatif's sentence commands where a consumer get to do an action or respond is purpose. Say frequent one to be utilized on sentence imperatif is say utilize  . Meanwhile imperatif's sentence researcher prohibition just finds 2 prohibition sentence which is avoid   and don't.
KONFLIK BATIN PEREMPUAN DALAM NOVEL ATAS SINGGASANA Karya Abidah El Khalieqy (Tinjauan Psikologi Sastra)
Authors: Agustiningsih Windi
Published: September 2020

Agustiningsih, Windi. 2013. Inner Conflict Prominent Women in Novels AtasSinggasana works Abidah El Khalieqy (Psychology Literature Review). Thesis.

The purpose of this research is to describe the structure of the novel, the inner conflictexperienced by women leaders, women leaders and solutions to overcome inner conflict.The method used in this research is descriptive qualitative method, which aims todescribe the inner conflict Prominent Women in the Novels Atas Singgasana worksAbidah El Khalieqy (Psychology Literature Review). The results showed that thestructure of the novel, the inner conflict experienced by women leaders, women leadersand solutions to overcome inner conflict found in every sentence, paragraph, or a chapterin the novel Atas Singgasana. The structure of the novel there are 20 data, there are 9inner conflict data, and solutions to resolve inner conflicts are 8 data
ANALISIS KOHESI DAN KOHERENSI DALAM WACANA MAJALAH ELSHINTA.COM PADA BERITA TOL BAKAUHENI-TERBANGGI BESAR SUDAH SIAP BEROPERASI 24 JAM
Authors: Hafiidha Sari Raras , Rahayu Titin
Published: September 2020

This study aims to describe the result of cohesion and coherence analysis as well as the latest news discourse on elshinta.com on Saturday 11 May 2019 in the reporting of the Bakauheni Toll Road Big Tol Ready to Operate 24 Hours. The method used in this study is descriptive, namely describing the result of the analysis found in this study. Thid type of research is qualitative research data is news that has been transcribed. The technique used to extract data is the note  and technique of note  taking. As for the data analysis technique used ini this study are based on dance theory, namely a complete and higest language above a sentence or clause with high cohesion that is continuous and has a final beginning andhas been manifestly conveyed trough oral and written. The result of the study are the: 1) use of cohesion and; 2) the use of coherence. Cohesion is a way that  composes discourse into the from of interrelationships  berween sentences or one component in  a solid  and  intact manner.  Element  of  cohension winch includes  references subsituas,  ellipses,  conjunctions, and lexical cohension which include repetition synonyms, antonyms,  colloquies, hyponyms, equivalence. While coherence is the compilation of content in the discourse element as a semantic organization,  which uses ideas in the logical sequence to achieve the intended speech correctly
Evaluation of the biological and wound healing activities of Centaurea virgata
Authors: AKSOY Halil
Published: September 2020

Objective: Plants have significant potential effects in treating the wound. The vast majority of plants are used by the public in the treatment of wounds. The aim of this study was to investigate the antioxidant and in vitro wound healing activities of Centaurea virgata (C. Virgata).

Methods: The antioxidant activities of extracts were examined by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and ABTS methods. The amount of total phenolic was determined using the Folin-Ciocalteu reagent (FCR) method. In addition, the antiproliferative activity of different extracts on fibroblast cells were performed by MTT method and in vitro wound healing activity of ethanol extract of C. Virgata was determined by scratch assay.

Results: Ethyl acetate extract of C. virgata (CVEA) had the highest DPPH radical scavenging activity with a IC50 value of 138.7 μg/mL. On the other hand, hexane (CVH) and aqueous ethanol (CVAE) revealed a very poor antioxidant activity with a IC50 values of 824,8 µg/mL and 610,3 ± 12,8 µg/mL, respectively. According to ABTS results, it was determined that the CVEA extract had stronger radical scavenging activity than the other extracts. On the other hand, among all of the extracts analysed, it was found that phenolic contents of CVEA extract had higher than other extracts. Except for CVAE extract, other extracts showed antiproliferative activity depending on the dose.

Conclusion: According to the obtained results, our finding suggests that CVAE extract has a migratory effect on fibroblasts and that CVAE might be a potential therapeutic agent for wound healing.
Development and Experimental Validation of TRNSYS Simulation Model for Heat Wheel Operated in Air Handling Unit
Authors: Al-Hyari Laith , Kassai Miklos
Published: September 2020

Reducing energy usage to save the environment is one of the main goals for the future. The energy losses in ventilation have a huge impact on energy consumption in buildings. In this work, the energy performance of a heat recovery wheel system equipped in an air handling unit was tested year-round, and the results compared with the simulation output for the system using TRNSYS software. The selected conditioned space was the staff offices of an H&M fashion shop, located in Eger, Hungary. Temperature, relative humidity, and air velocity sensors were placed at the wheel inlet and outlet sections to record data and determine the annual energy saving. The results revealed a good agreement between the measured and simulated results.
Special Issue “Selected Papers from the 2018 IEEE International Conference on High Voltage Engineering (ICHVE 2018)”
Authors: Gonos Ioannis F. , Fofana Issouf
Published: September 2020

The 2018 IEEE International Conference on High Voltage Engineering and Application (ICHVE 2018) was organized by the National Technical University of Athens, Greece and endorsed by the IEEE Dielectrics and Electrical Insulation Society [...]
Efficiency versus Equity in Spatial Siting of Electricity Generation: Citizen Preferences in a Serious Board Game in Switzerland
Authors: Steinberger Franziska , Minder Tobias , Trutnevyte Evelina
Published: September 2020

Energy transitions around the world will change the spatial fingerprint of the electricity sector, but there is a lack of studies on citizen preferences for siting the future mix of electricity technologies. Using the case of Switzerland in 2035, we present a serious board game to form and elicit citizen preferences for spatial siting of a full mix of electricity technologies and we test this game with 44 participants in the city of Zurich. The game proves to help elicit valid preferences of the participants and lead to measurable learning effects about this complex, multi-dimensional topic. The results show that these 44 participants prefer a diverse mix of renewable technologies for Switzerland in 2035. In terms of siting, these participants consistently choose the efficiency strategy, where new plants are concentrated in the areas where they produce most electricity at least cost, in contrast to the strategy of regional equity, where all Swiss regions would equally build new generation and share the benefits and burdens of the energy transition.
A Novel Deep Learning Approach for Wind Power Forecasting Based on WD-LSTM Model
Authors: Liu Bingchun , Zhao Shijie , Yu Xiaogang , Zhang Lei , Wang Qingshan
Published: September 2020

Wind power generation is one of the renewable energy generation methods which maintains good momentum of development at present. However, its extremely intense intermittences and uncertainties bring great challenges to wind power integration and the stable operation of wind power grids. To achieve accurate prediction of wind power generation in China, a hybrid prediction model based on the combination of Wavelet Decomposition (WD) and Long Short-Term Memory neural network (LSTM) is constructed. Firstly, the nonstationary time series is decomposed into multidimensional components by WD, which can effectively reduce the volatility of the original time series and make them more stable and predictable. Then, the components of the original time series after WD are used as input variables of LSTM to predict the national wind power generation. Forty points were used, 80% as training samples and 20% as testing samples. The experimental results show that the MAPE of WD-LSTM is 5.831, performing better than other models in predicting wind power generation in China. In addition, the WD-LSTM model was used to predict the wind power generation in China under different development trends in the next two years.
Adaptive Square-Root Unscented Kalman Filter-Based State-of-Charge Estimation for Lithium-Ion Batteries with Model Parameter Online Identification
Authors: Ouyang Quan , Ma Rui , Wu Zhaoxiang , Xu Guotuan , Wang Zhisheng
Published: September 2020

The state-of-charge (SOC) is a fundamental indicator representing the remaining capacity of lithium-ion batteries, which plays an important role in the battery’s optimized operation. In this paper, the model-based SOC estimation strategy is studied for batteries. However, the battery’s model parameters need to be extracted through cumbersome prior experiments. To remedy such deficiency, a recursive least squares (RLS) algorithm is utilized for model parameter online identification, and an adaptive square-root unscented Kalman filter (SRUKF) is designed to estimate the battery’s SOC. As demonstrated in extensive experimental results, the designed adaptive SRUKF combined with RLS-based model identification is a promising SOC estimation approach. Compared with other commonly used Kalman filter-based methods, the proposed algorithm has higher precision in the SOC estimation.
Recognition of Variable-Speed Equipment in an Air-Conditioning System Using Numerical Analysis of Energy-Consumption Data
Authors: Ma Rongjiang , Wang Xianlin , Shan Ming , Yu Nanyang , Yang Shen
Published: September 2020

Motor-driven equipment (ME) is one of the key components in an air-conditioning system, which contributes to the vast majority of the total energy consumption by air-conditioning systems. Distinguishing variable- and constant-speed equipment is important since the energy simulation models of the two types differ. Traditionally, types of ME are known in advance, and energy consumption data are consequently analyzed. However, in the application scenarios of energy consumption data mining, precedent information on the ME type could be missing. Thus, this study applies this process in reverse, providing new insight into energy consumption data of ME to recognize variable-speed ME in an air-conditioning system. The energy consumption data of ME in an air-conditioning system implemented in a commercial building were collected and numerically analyzed. A proposed simple parameter, coefficient of the median, and several numerical parameters were calculated and used to distinguish variable- from constant-speed ME. Results showed that the energy consumption data distributions of the two types of ME differed. The proposed coefficient of the median could successfully distinguish variable- from constant-speed ME, and it could be applied as an important step in energy consumption data mining of air-conditioning systems.
A Coupling Diagnosis Method for Sensor Faults Detection, Isolation and Estimation of Gas Turbine Engines
Authors: Zhu Linhai , Liu Jinfu , Ma Yujia , Zhou Weixing , Yu Daren
Published: September 2020

In this paper a novel fault detection, isolation, and identification (FDI&E) scheme using a coupling diagnosis method with the integration of the model-based method and unsupervised learning algorithm is proposed and developed for monitoring gas turbine sensor faults, which represents an integration of Square Root Cubature Kalman Filters (SRCKF) and an improved Density-Based Spatial Clustering of Application with Noise (DBSCAN) algorithm. A detection indicator produced by SRCKF with a specific hypothesis is used for extracting sensor fault features against process and measurement noise, as well as operating conditions. Then, an improved DBSCAN is implemented based on a voting scheme to detect and isolate the faulty sensors. Finally, a residual-based fault estimation scheme is proposed to track sensor fault evolution and help to judge the types of faults. Moreover, the observability of the model involved is analyzed to verify the stable operation of the FDI&E scheme. Various experiments for single and concurrent sensor fault scenarios in a dual-spool gas turbine prototype during a whole flight mission are conducted to demonstrate the effectiveness of the proposed FDI&E scheme. Moreover, comparative studies confirm the superiority of our proposed FDI&E scheme than the existing methods in terms of promptness and robustness of the sensor FDI.
Prenatal Maternal Cortisol Levels and Infant Birth Weight in a Predominately Low-Income Hispanic Cohort
Authors: Peterson Alicia , Toledo-Corral Claudia M. , Chavez Thomas , Naya Christine , Johnson Mark , Eckel Sandrah , Lerner Deborah , Grubbs Brendan , Farzan Shohreh , Dunton Genevieve , Bastain Theresa , Breton Carrie
Published: September 2020

Infant birth weight influences numerous health outcomes throughout the life course including childhood obesity and metabolic morbidities. Maternal experience of stress, both before and during pregnancy, has been hypothesized to influence fetal growth and birth outcomes. However, these associations currently are not fully understood, due to conflicting results in the published literature. Salivary cortisol is often used as a biological biomarker to assess the diurnal pattern of the hypothalamic–pituitary–adrenal axis (HPA-axis) functioning. Cortisol metrics include both the total cortisol concentration secreted during waking hours, reflected by the area under the curve (AUC), and cortisol dynamics, which include the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). This study examined the association of these cortisol metrics measured during the third trimester of pregnancy and infant birth weight among 240 mother-infant dyads participating in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study, which is predominately comprised of Hispanic low-income women. There were no significant associations with the maternal biological stress response and infant birth weight in this study. More research is needed in larger studies to better understand how the biological stress response influences birth weight in populations facing health disparities.
Can Physical and/or Sexual Abuse Play a Role in the Female Choice of a Partner? A Cross-Sectional, Correlational Pilot Study
Authors: Limoncin Erika , Solano Caterina , Ciocca Giacomo , Mollaioli Daniele , Colonnello Elena , Sansone Andrea , Nimbi Filippo Maria , Simonelli Chiara , Tambelli Renata , Jannini Emmanuele Angelo
Published: September 2020

The present study aims to evaluate the relationship in women between a history of physical/sexual abuse and the preferences regarding the choice of a partner for a short/long-term relationship in terms of male facial dimorphism, and to assess their sexual functioning. We enrolled 48 abused women and 60 non-abused women. Facial preferences were evaluated with the Morphing test. Sexual functioning was measured with the Female Sexual Function Index (FSFI). Regarding the choice for a short-term partner, abused and non-abused women did not show any differences, and both groups chose a less masculine male face. On the other hand, regarding the choice for a long-term partner, abused women showed a preference for an average male face, whilst non-abused women preferred a less masculine face. The sexual functioning of abused women was found significantly dysfunctional in all domains of the FSFI. These data, generated from a small but highly selected cohort, demonstrated that physical/sexual abuse may be associated with a more rational and conscious choice of a male partner for a long-term relationship, but not with an instinctive one, as the choice of an occasional partner. In addition, the sexual functioning of abused women appears to be compromised by the traumatic experience.
Plant Elongator—Protein Complex of Diverse Activities Regulates Growth, Development, and Immune Responses
Authors: Jarosz Magdalena , Van Lijsebettens Mieke , Woloszynska Magdalena
Published: September 2020

Contrary to the conserved Elongator composition in yeast, animals, and plants, molecular functions and catalytic activities of the complex remain controversial. Elongator was identified as a component of elongating RNA polymerase II holoenzyme in yeast, animals, and plants. Furthermore, it was suggested that Elonagtor facilitates elongation of transcription via histone acetyl transferase activity. Accordingly, phenotypes of Arabidopsis elo mutants, which show development, growth, or immune response defects, correlate with transcriptional downregulation and the decreased histone acetylation in the coding regions of crucial genes. Plant Elongator was also implicated in other processes: transcription and processing of miRNA, regulation of DNA replication by histone acetylation, and acetylation of alpha-tubulin. Moreover, tRNA modification, discovered first in yeast and confirmed in plants, was claimed as the main activity of Elongator, leading to specificity in translation that might also result indirectly in a deficiency in transcription. Heterologous overexpression of individual Arabidopsis Elongator subunits and their respective phenotypes suggest that single Elongator subunits might also have another function next to being a part of the complex. In this review, we shall present the experimental evidence of all molecular mechanisms and catalytic activities performed by Elongator in nucleus and cytoplasm of plant cells, which might explain how Elongator regulates growth, development, and immune responses.
In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins
Authors: Göttel Celina , Niesen Sonja , Daub Vanessa , Werle Theresa , Bakuradze Tamara , Winterhalter Peter , Richling Elke
Published: September 2020

Phosphodiesterases (PDEs) are essential enzymes for the regulation of pathways mediated by cyclic adenosine monophosphate (cAMP). Secondary plant compounds like anthocyanins (ACs) can inhibit PDE activity and, consequently, may be beneficial for lipid metabolism. This study investigated 18 AC-rich juice extracts and pure reference compounds from red fruits for potential inhibitory effects on PDE 3B activity. Extracts were obtained through adsorption on Amberlite® XAD 7 resin. Based on this screening, the chokeberry, blueberry, pomegranate, and cranberry extracts were active, with half maximal inhibitory concentrations (IC50) ranging from 163 ± 3 µg/mL to 180 ± 3 µg/mL. The ACs in these extracts, peonidin-3-glucoside and cyanidin-3-arabinoside, were the most active single compounds (IC50 = 56 ± 20 µg/mL, 108 ± 6 µg/mL). All extracts comprised high amounts of phenolic compounds, as determined by the Folin–Ciocalteu assay, ranging from 39.8 ± 1.5 to 73.5 ± 4.8 g gallic acid equivalents (GAE)/100 g extract. Pomegranate and chokeberry extracts exhibited the largest amounts of polyphenols (72.3 ± 0.7 g GAE/100 g, 70.6 ± 4.1 g GAE/100 g, respectively). Overall, our results showed that fruit juice extracts and their ACs can inhibit PDE activity. Any potential health benefits in vivo will be investigated in the future.
Oxidative Stress and DNA Damage in Chronic Disease and Environmental Studies
Authors: Peluso Marco , Russo Valentina , Mello Tommaso , Galli Andrea
Published: September 2020

Humans are continually exposed to a large number of environmental carcinogens [...]
Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis
Authors: Dash Banaja P. , Naumann Marcel , Sterneckert Jared , Hermann Andreas
Published: September 2020

Amyotropic lateral sclerosis (ALS) is a lethally progressive and irreversible neurodegenerative disease marked by apparent death of motor neurons present in the spinal cord, brain stem and motor cortex. While more and more gene mutants being established for genetic ALS, the vast majority suffer from sporadic ALS (>90%). It has been challenging, thus, to model sporadic ALS which is one reason why the underlying pathophysiology remains elusive and has stalled the development of therapeutic strategies of this progressive motor neuron disease. To further unravel these pathological signaling pathways, human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from FUS- and SOD1 ALS patients and healthy controls were systematically compared to independent published datasets. Here through this study we created a gene profile of ALS by analyzing the DEGs, the Kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome and the transcription factor profiles (TF) that would identify altered molecular/functional signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs). Our findings suggest that FUS and SOD1 may develop from dysregulation in several unique pathways and herpes simplex virus (HSV) infection was among the topmost predominant cellular pathways connected to FUS and not to SOD1. In contrast, SOD1 is mainly characterized by alterations in the metabolic pathways and alterations in the neuroactive-ligand–receptor interactions. This suggests that different genetic ALS forms are singular diseases rather than part of a common spectrum. This is important for patient stratification clearly pointing towards the need for individualized medicine approaches in ALS.
Alternating Electric Fields Modify the Function of Human Osteoblasts Growing on and in the Surroundings of Titanium Electrodes
Authors: Sahm Franziska , Ziebart Josefin , Jonitz-Heincke Anika , Hansmann Doris , Dauben Thomas , Bader Rainer
Published: September 2020

Endogenous electric fields created in bone tissue as a response to mechanical loading are known to influence the activity and differentiation of bone and precursor cells. Thus, electrical stimulation offers an adjunct therapy option for the promotion of bone regeneration. Understanding the influence of electric fields on bone cell function and the identification of suitable electrical stimulation parameters are crucial for the clinical success of stimulation therapy. Therefore, we investigated the impact of alternating electric fields on human osteoblasts that were seeded on titanium electrodes, which delivered the electrical stimulation. Moreover, osteoblasts were seeded on collagen-coated coverslips near the electrodes, representing the bone stock surrounding the implant. Next, 0.2 V, 1.4 V, or 2.8 V were applied to the in vitro system with 20 Hz frequency. After one, three, and seven days, the osteoblast morphology and expression of osteogenic genes were analysed. The actin organisation, as well as the proliferation, were not affected by the electrical stimulation. Changes in the gene expression and protein accumulation after electrical stimulation were voltage-dependent. After three days, the osteogenic gene expression and alkaline phosphatase activity were up to 2.35-fold higher following the electrical stimulation with 0.2 V and 1.4 V on electrodes and coverslips compared to controls. Furthermore, collagen type I mRNA, as well as the amount of the C-terminal propeptide of collagen type I were increased after the stimulation with 0.2 V and 1.4 V, while the higher electrical stimulation with 2.8 V led to decreased levels, especially on the electrodes.
Investigation of Biofilms Formed on Steelmaking Slags in Marine Environments for Water Depuration
Authors: Ogawa Akiko , Tanaka Reiji , Hirai Nobumitsu , Ochiai Tatsuki , Ohashi Ruu , Fujimoto Karin , Akatsuka Yuka , Suzuki Masanori
Published: September 2020

Steelmaking slags are a promising resource as artificial seaweed beds for the reconstitution of marine environments. To grow seaweed well, the formation of biofilms is an essential process in biofouling. This study focused on the formation of initial biofilms on steelmaking slag samples and analyzed the resulting bacterial communities using the next-generation sequencing technique. Three types of steelmaking slag were submerged in an area of Ise Bay in Mie Prefecture, Japan, for 3 and 7 days in the summer and winter seasons to allow the formation of biofilms. The bacterial communities of these biofilms were richer in sulfur-oxidizing bacteria compared to the biofilms formed on polyurethane sponges. It was found that Helicobacteraceae dominantly grew on the biofilms formed on the slag samples. This shows that steelmaking slags have potential to be used as artificial seaweed beds and marine water purifiers.
Immunohistochemistry and Mutation Analysis of SDHx Genes in Carotid Paragangliomas
Authors: Snezhkina Anastasiya V. , Kalinin Dmitry V. , Pavlov Vladislav S. , Lukyanova Elena N. , Golovyuk Alexander L. , Fedorova Maria S. , Pudova Elena A. , Savvateeva Maria V. , Stepanov Oleg A. , Poloznikov Andrey A. , Demidova Tatiana B. , Melnikova Nataliya V. , Dmitriev Alexey A. , Krasnov George S. , Kudryavtseva Anna V.
Published: September 2020

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors often associated with mutations in SDHx genes. The immunohistochemistry of succinate dehydrogenase (SDH) subunits has been considered a useful instrument for the prediction of SDHx mutations in paragangliomas/pheochromocytomas. We compared the mutation status of SDHx genes with the immunohistochemical (IHC) staining of SDH subunits in CPGLs. To identify pathogenic/likely pathogenic variants in SDHx genes, exome sequencing data analysis among 42 CPGL patients was performed. IHC staining of SDH subunits was carried out for all CPGLs studied. We encountered SDHx variants in 38% (16/42) of the cases in SDHx genes. IHC showed negative (5/15) or weak diffuse (10/15) SDHB staining in most tumors with variants in any of SDHx (94%, 15/16). In SDHA-mutated CPGL, SDHA expression was completely absent and weak diffuse SDHB staining was detected. Positive immunoreactivity for all SDH subunits was found in one case with a variant in SDHD. Notably, CPGL samples without variants in SDHx also demonstrated negative (2/11) or weak diffuse (9/11) SDHB staining (42%, 11/26). Obtained results indicate that SDH immunohistochemistry does not fully reflect the presence of mutations in the genes; diagnostic effectiveness of this method was 71%. However, given the high sensitivity of SDHB immunohistochemistry, it could be used for initial identifications of patients potentially carrying SDHx mutations for recommendation of genetic testing.
The Interplay between Toxic and Essential Metals for Their Uptake and Translocation Is Likely Governed by DNA Methylation and Histone Deacetylation in Maize
Authors: Shafiq Sarfraz , Ali Asim , Sajjad Yasar , Zeb Qudsia , Shahzad Muhammad , Khan Abdul Rehman , Nazir Rashid , Widemann Emilie
Published: September 2020

The persistent nature of lead (Pb) and cadmium (Cd) in the environment severely affects plant growth and yield. Conversely, plants acquire zinc (Zn) from the soil for their vital physiological and biochemical functions. However, the interplay and coordination between essential and toxic metals for their uptake and translocation and the putative underlying epigenetic mechanisms have not yet been investigated in maize. Here, we report that the presence of Zn facilitates the accumulation and transport of Pb and Cd in the aerial parts of the maize plants. Moreover, the Zn, Pb, and Cd interplay specifically interferes with the uptake and translocation of other divalent metals, such as calcium and magnesium. Zn, Pb, and Cd, individually and in combinations, differentially regulate the expression of DNA methyltransferases, thus alter the DNA methylation levels at the promoter of Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) genes to regulate their expression. Furthermore, the expression of histone deacetylases (HDACs) varies greatly in response to individual and combined metals, and HDACs expression showed a negative correlation with ZIP transporters. Our study highlights the implication of DNA methylation and histone acetylation in regulating the metal stress tolerance dynamics through Zn transporters and warns against the excessive use of Zn fertilizers in metal contaminated soils.
Chondroprotective Actions of Selective COX-2 Inhibitors In Vivo: A Systematic Review
Authors: Timur Ufuk Tan , Caron Marjolein M. J. , Jeuken Ralph M. , Bastiaansen-Jenniskens Yvonne M. , Welting Tim J. M. , van Rhijn Lodewijk W. , van Osch Gerjo J. V. M. , Emans Pieter J.
Published: September 2020

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.
Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines
Authors: Shin Jihun , Song Hwa Young , Lee Mina
Published: September 2020

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.
Antimicrobial Peptides as New Combination Agents in Cancer Therapeutics: A Promising Protocol against HT-29 Tumoral Spheroids
Authors: Raileanu Mina , Popescu Aurel , Bacalum Mihaela
Published: September 2020

Antimicrobial peptides are molecules synthetized by a large variety of organisms as an innate defense against pathogens. These natural compounds have been identified as promising alternatives to widely used molecules to treat infections and cancer cells. Antimicrobial peptides could be viewed as future chemotherapeutic alternatives, having the advantage of low propensity to drug resistance. In this study, we evaluated the efficiency of the antimicrobial peptide gramicidin A (GA) and the anticancer drug, doxorubicin (Doxo) against the spheroids from colorectal cancer cells (HT-29). The two drugs were applied separately against HT-29 spheroids as well as together to determine if they can act synergistically. The spheroid evolution, cell viability, and ATP levels were monitored at 24 and 48 h after the applied treatments. The results show significant drops in cell viability and cellular ATP levels for all the experimental treatments. The simultaneous use of the two compounds (GA and Doxo) seems to cause a synergistic effect against the spheroids.
IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection
Authors: Ren Heather M. , Lukacher Aron E.
Published: September 2020

CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer by mitigating generation of exhausted T cells (TEX). CD4 T cell help is also required for establishing and maintaining tissue-resident memory T cells (TRM), the nonrecirculating memory T cell subset parked in nonlymphoid tissues to provide frontline defense against reinvading pathogens. Interleukin (IL)-21 is the signature cytokine secreted by follicular helper CD4 T cells (TFH) to drive B cell expansion and differentiation in germinal centers to mount high-affinity, isotype class-switched antibodies. In several infection models, IL-21 has been identified as the CD4 T help needed for formation and survival of TRM and TEX. In this review, we will explore the different memory subsets of CD8 T cells in persistent infections, the metabolic profiles associated with each, and evidence documenting the importance of CD4 T cell-derived IL-21 in regulating CD8 TRM and TEX development, homeostasis, and function.
Double-Stranded RNA Binding Proteins in Serum Contribute to Systemic RNAi Across Phyla—Towards Finding the Missing Link in Achelata
Authors: Banks Thomas M. , Wang Tianfang , Fitzgibbon Quinn P. , Smith Gregory G. , Ventura Tomer
Published: September 2020

RNA interference (RNAi) has become a widely utilized method for studying gene function, yet despite this many of the mechanisms surrounding RNAi remain elusive. The core RNAi machinery is relatively well understood, however many of the systemic mechanisms, particularly double-stranded RNA (dsRNA) transport, are not. Here, we demonstrate that dsRNA binding proteins in the serum contribute to systemic RNAi and may be the limiting factor in RNAi capacity for species such as spiny lobsters, where gene silencing is not functional. Incubating sera from a variety of species across phyla with dsRNA led to a gel mobility shift in species in which systemic RNAi has been observed, with this response being absent in species in which systemic RNAi has never been observed. Proteomic analysis suggested lipoproteins may be responsible for this phenomenon and may transport dsRNA to spread the RNAi signal systemically. Following this, we identified the same gel shift in the slipper lobster Thenus australiensis and subsequently silenced the insulin androgenic gland hormone, marking the first time RNAi has been performed in any lobster species. These results pave the way for inducing RNAi in spiny lobsters and for a better understanding of the mechanisms of systemic RNAi in Crustacea, as well as across phyla.
4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model
Authors: Wu Chia-Hsin , Ou Ching-Huei , Yen I-Chuan , Lee Shih-Yu
Published: September 2020

Astronauts suffer from 1–2% bone loss per month during space missions. Targeting osteoclast differentiation has been regarded as a promising strategy to prevent osteoporosis in microgravity (μXg). 4-acetylantroquinonol B (4-AAQB), a ubiquinone from Antrodia cinnamomea, has shown anti-inflammatory and anti-hepatoma activities. However, the effect of 4-AAQB on μXg-induced osteoclastogenesis remains unclear. In this study, we aimed to explore the mechanistic impact of 4-AAQB on osteoclast formation under μXg conditions. The monocyte/macrophage-like cell line RAW264.7 was exposed to simulated μXg (Rotary Cell Culture System; Synthecon, Houston, TX, USA) for 24 h and then treated with 4-AAQB or alendronate (ALN) and osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclastogenesis, bone resorption activity, and osteoclast differentiation-related signaling pathways were analyzed using tartrate-resistant acid phosphatase (TRAP) staining, actin ring fluorescent staining, bone resorption, and western blotting assays. Based on the results of TRAP staining, actin ring staining, and bone resorption assays, we found that 4-AAQB significantly inhibited μXg-induced osteoclast differentiation. The critical regulators of osteoclast differentiation, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, and dendritic cell-specific transmembrane protein (DC-STAMP), were consistently decreased. Meanwhile, osteoclast apoptosis and cell cycle arrest were also observed along with autophagy suppression. Interestingly, the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) showed similar effects to 4-AAQB. In conclusion, we suggest that 4-AAQB may serve as a potential agent against μXg-induced osteoclast formation.
Echinocandins as Biotechnological Tools for Treating Candida auris Infections
Authors: Cândido Elizabete de Souza , Affonseca Flávia , Cardoso Marlon Henrique , Franco Octavio Luiz
Published: September 2020

Candida auris has been reported in the past few years as an invasive fungal pathogen of high interest. Its recent emergence in healthcare-associated infections triggered the efforts of researchers worldwide, seeking additional alternatives to the use of traditional antifungals such as azoles. Lipopeptides, specially the echinocandins, have been reported as an effective approach to control pathogenic fungi. However, despite its efficiency against C. auris, some isolates presented echinocandin resistance. Thus, therapies focused on echinocandins’ synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections.