bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Dietary Supplementation of Lactic Acid Bacteria Fermented Rapeseed with or without Macroalgae on Performance and Health of Piglets Following Omission of Medicinal Zinc from Weaner Diets
Authors: Satessa Gizaw D. , Tamez-Hidalgo Paulina , Hui Yan , Cieplak Tomasz , Krych Lukasz , Kjærulff Søren , Brunsgaard Grete , Nielsen Dennis S. , Nielsen Mette O.
Published: January 2020

The feeding of medicinal zinc oxide (ZnO) to weaner piglets will be phased out after 2022 in Europe, leaving pig producers without options to manage post-weaning disorders. This study assessed whether rapeseed meal, fermented alone (FRM) or co-fermented with a single (Ascophylum nodosum; FRMA), or two (A. nodossum and Saccharina latissima; FRMAS) brown macroalagae species, could improve weaner piglet performance and stimulate intestinal development as well as maturation of gut microbiota in the absence of in-feed zinc. Weaned piglets (n = 1240) were fed, during 28–85 days of age, a basal diet with no additives (negative control; NC), 2500 ppm in-feed ZnO (positive control; PC), FRM, FRMA or FRMAS. Piglets fed FRM and FRMA had a similar or numerically improved, respectively, production performance compared to PC piglets. Jejunal villus development was stimulated over NC in PC, FRM and FRMAS (gender-specific). FRM enhanced colon mucosal development and reduced signs of intestinal inflammation. All fermented feeds and PC induced similar changes in the composition and diversity of colon microbiota compared to NC. In conclusion, piglet performance, intestinal development and health indicators were sustained or numerically improved when in-feed zinc was replaced by FRM.
Large-Scale Screening and Machine Learning to Predict the Computation-Ready, Experimental Metal-Organic Frameworks for CO2 Capture from Air
Authors: Deng Xiaomei , Yang Wenyuan , Li Shuhua , Liang Hong , Shi Zenan , Qiao Zhiwei
Published: January 2020

The rising level of CO2 in the atmosphere has attracted attention in recent years. The technique of capturing CO2 from higher CO2 concentrations, such as power plants, has been widely studied, but capturing lower concentrations of CO2 directly from the air remains a challenge. This study uses high-throughput computer (Monte Carlo and molecular dynamics simulation) and machine learning (ML) to study 6013 computation-ready, experimental metal-organic frameworks (CoRE-MOFs) for CO2 adsorption and diffusion properties in the air with very low concentrations of CO2. First, the law influencing CO2 adsorption and diffusion in air is obtained as a structure-performance relationship, and then the law influencing the performance of CO2 adsorption and diffusion in air is further explored by four ML algorithms. Random forest (RF) was considered the optimal algorithm for prediction of CO2 selectivity, with an R value of 0.981, and this algorithm was further applied to analyze the relative importance of each metal-organic framework (MOF) descriptor quantitatively. Finally, 14 MOFs with the best properties were successfully screened out, and it was found that a key to capturing a low concentration CO2 from the air was the diffusion performance of CO2 in MOFs. When the pore-limiting diameter (PLD) of a MOF was closer to the CO2 dynamic diameter, this MOF could possess higher CO2 diffusion separation selectivity. This study could provide valuable guidance for the synthesis of new MOFs in experiments that capture directly low concentration CO2 from the air.
Chitooligosaccharide as A Possible Replacement for Sulfur Dioxide in Winemaking
Authors: Hao Zhenming , Zhang Yanrong , Sun Zhen , Li Xianzhen
Published: January 2020

Sulfur dioxide (SO2) has been used for centuries as a preservative in winemaking. However, the addition of SO2 is associated with allergic reactions and can negatively affect wine quality. In our work, chitooligosaccharide (COS) was applied as an alternative to SO2 in winemaking, and its antimicrobial activity during winemaking was investigated in comparison with the action of SO2. The optimal concentration of COS was identified as 500 mg/L. The antimicrobial effect of COS was evaluated using known and our own separated wine spoilage organisms. The antimicrobial effect of 500 mg/L COS was found to be comparable with that of 100 mg/L SO2. Furthermore, using 500 mg/L COS as an additive during winemaking did notinfluence the cell growth of Saccharomyces cerevisiae. Therefore, COS can be used as an additive in winemaking.
Microbiota Alterations in Gastrointestinal Cancers
Authors: Karwowska Zuzanna , Szemraj Janusz , Karwowski Bolesław
Published: January 2020

Commensal microbiota plays a critical role in the maintenance of human health. Microbes influence energy metabolism and nutrient absorption and help defend the host organism against pathogens. The composition of the gut microbiota is delicately balanced, and any alterations may lead to proinflammatory immune responses and initiation of disease processes, including cancer. Experimental evidence indicates that the human intestinal microbiota can influence tumour development and progression in the gastrointestinal tract by damaging DNA, activation of oncogenic signaling pathways, production of tumour-promoting metabolites, and suppression of the anti-tumour immune response. The aim of this article was to outline differences in human microbiota between healthy subjects and patients with gastrointestinal malignancies such as esophageal, stomach, liver, biliary tract, pancreas and colon inflammations, and cancers. A better understanding of microbiota changes in various gastrointestinal malignancies will enable a greater insight into the relationship between human microbiota composition and cancer development.
Effective Feature Selection Method for Deep Learning-Based Automatic Modulation Classification Scheme Using Higher-Order Statistics
Authors: Lee Sang Hoon , Kim Kwang-Yul , Shin Yoan
Published: January 2020

Recently, in order to satisfy the requirements of commercial communication systems and military communication systems, automatic modulation classification (AMC) schemes have been considered. As a result, various artificial intelligence algorithms such as a deep neural network (DNN), a convolutional neural network (CNN), and a recurrent neural network (RNN) have been studied to improve the AMC performance. However, since the AMC process should be operated in real time, the computational complexity must be considered low enough. Furthermore, there is a lack of research to consider the complexity of the AMC process using the data-mining method. In this paper, we propose a correlation coefficient-based effective feature selection method that can maintain the classification performance while reducing the computational complexity of the AMC process. The proposed method calculates the correlation coefficients of second, fourth, and sixth-order cumulants with the proposed formula and selects an effective feature according to the calculated values. In the proposed method, the deep learning-based AMC method is used to measure and compare the classification performance. From the simulation results, it is indicated that the AMC performance of the proposed method is superior to the conventional methods even though it uses a small number of features.
Investigating the Learning Process of Folk Dances Using Mobile Augmented Reality
Authors: Kico Iris , Liarokapis Fotis
Published: January 2020

Learning how to dance is not an easy task and traditional teaching methods are the main approach. Digital technologies (such as video recordings of dances) have already been successfully used in combination with the traditional methods. However, there are other emerging technologies such as virtual and augmented reality that have the potential of providing greater assistance, in order to speed up the process as well as assisting the learners. This paper presents a prototype mobile augmented reality application for assisting the process of learning folk dances. Initially, a folk dance was digitized based on recordings from professional dancers. Avatar representations (of either male or female) are synchronized with the digital representation of the dance. To assess the effectiveness of mobile augmented reality, it was comparatively evaluated with a large back-projection system in laboratory conditions. Twenty healthy participants took part in the study, and their movements were captured using motion capture system and then compared with the recordings from the professional dancers. Experimental results indicate that augmented reality (AR) application has the potential to be used for learning process.
An IoT Based Mobile Augmented Reality Application for Energy Visualization in Buildings Environments
Authors: Alonso-Rosa Manuel , Gil-de-Castro Aurora , Moreno-Munoz Antonio , Garrido-Zafra Joaquín , Gutierrez-Ballesteros Elena , Cañete-Carmona Eduardo
Published: January 2020

Augmented reality (AR) improves how we acquire, understand, and display information without distracting us from the real world. These technologies can be used in different applications and industries as they can incorporate domain-specific visualizations on a real-world screen. Mobile augmented reality (MAR) essentially consists of superimposing virtual elements over real objects on the screen, to give added value and enrich the interaction with reality. In numerous plants, it is being used for maintenance and repair tasks, as well as training. The Internet of Things (IoT) is increasingly pervading every aspect of our lives, including the power infrastructure of our buildings. IoT-enabled devices offer many connectivity options for helping supervise all-important energy assets. Aggregating data to cloud-based platforms enables operations teams to have on-time information access to make fast decisions and have a fast response regarding energy use, while maintenance teams keep on top of the appliance power quality and reliability needed by using MAR. This paper presents a novel approximation for visualizing appliance-related power quality to enhance awareness about the consumed electricity. A combined solution of MAR with IoT technologies is employed. Engineered solutions’ hands-free way to get data about surrounding appliances reduces the complexity, saves energy, and speeds up the operations. An innovative way to measure things at the right time leads to a competitive advantage.
PM10 and PM2.5 Qualitative Source Apportionment Using Selective Wind Direction Sampling in a Port-Industrial Area in Civitavecchia, Italy
Authors: Soggiu Maria Eleonora , Inglessis Marco , Gagliardi Roberta Valentina , Settimo Gaetano , Marsili Giovanni , Notardonato Ivan , Avino Pasquale
Published: January 2020

The possibility to discriminate between different emission sources and between natural and anthropogenic contributions is a key issue for planning efficient air pollution reduction and mitigation strategies. Moreover, the knowledge of the particulate matter (PM) chemical composition for the different size fractions is recognized as increasingly important, in particular with respect to health effects of exposed population. This study is focused on the characterization of PM10 and PM2.5 main sources located in the Civitavecchia harbor-industrial area (Central Italy), namely a large coal-fired power plant, a natural gas power plant, the harbor area, the vehicular traffic (due to both the local traffic and the highway crossing the area) and small industrial activities. The approach was based on PM10/PM2.5 samples monthly collected for one year and a further relative chemical characterization of organic and inorganic fractions. Wind-select sensors, allowing a selective PM10 and PM2.5 sampling downwind to specific emission sources, were used for the overall sampling. This methodology manages to explain specific emission patterns and to assess the concentration levels of the micro pollutants emitted by local sources and particularly toxic for health. A descriptive statistical analysis of data was performed, also verifying the occurrence of legislative threshold exceedances. Moreover, in order to highlight the contribution of specific sources, the differences in the measured micro pollutants concentrations between wind directions, PM size fractions and sampling sites have been investigated, as well as the seasonal trends of pollutants concentrations. These results allow to highlight that the applied methodology represents a valid support in source apportionment studies.
Sodium Resonance Wind-Temperature Lidar at PFRR: Initial Observations and Performance
Authors: Li Jintai , Williams Bifford P. , Alspach Jennifer H. , Collins Richard L.
Published: January 2020

A narrowband sodium resonance wind-temperature lidar (SRWTL) has been deployed at Poker Flat Research Range, Chatanika, Alaska (PFRR, 65° N, 147° W). Based on the Weber narrowband SRWTL, the PFRR SRWTL transmitter was upgraded with a state-of-the-art solid-state tunable diode laser as the seed laser. The PFRR SRWTL currently makes simultaneous measurements in the zenith and 20° off-zenith towards the north with two transmitted beams and two telescopes. Initial results for both nighttime and daytime measurements are presented. We review the performance of the PFRR SRWTL in terms of seven previous and currently operating SRWTLs. The transmitted power from the pulsed dye amplifier (PDA) is comparable with other SRWTL systems (900 mW). However, while the efficiency of the seeding and frequency shifting is comparable to other SRWTLs the efficiency of the pumping is lower. The uncertainties of temperature and wind measurements induced by photon noise at the peak of the layer with a 5 min, 1 km resolution are estimated to be ~1 K and 2 m/s for nighttime conditions, and 10 K and 6 m/s for daytime conditions. The relative efficiency of the zenith receiver is comparable to other SRWTLs (90–97%), while the efficiency of the north off-zenith receiver needs further optimization. An upgrade of the PFRR SRWTL to a full three-beam system with zenith, northward and eastward measurements is in progress.
Synthesis of a NiMoO4/3D-rGO Nanocomposite via Starch Medium Precipitation Method for Supercapacitor Performance
Authors: Arshadi Rastabi Shahrzad , Sarraf Mamoory Rasoul , Blomquist Nicklas , Phadatare Manisha , Olin Håkan
Published: January 2020

This paper presents research on the synergistic effects of nickel molybdate and reduced graphene oxide as a nanocomposite for further development of energy storage systems. An enhancement in the electrochemical performance of supercapacitor electrodes occurs by synthesizing highly porous structures and achieving more surface area. In this work, a chemical precipitation technique was used to synthesize the NiMoO4/3D-rGO nanocomposite in a starch media. Starch was used to develop the porosities of the nanostructure. A temperature of 350 °C was applied to transform graphene oxide sheets to reduced graphene oxide and remove the starch to obtain the NiMoO4/3D-rGO nanocomposite with porous structure. The X-ray diffraction pattern of the NiMoO4 nano particles indicated a monoclinic structure. Also, the scanning electron microscope observation showed that the NiMoO4 NPs were dispersed across the rGO sheets. The electrochemical results of the NiMoO4/3D-rGO electrode revealed that the incorporation of rGO sheets with NiMoO4 NPs increased the capacity of the nanocomposite. Therefore, a significant increase in the specific capacity of the electrode was observed with the NiMoO4/3D-rGO nanocomposite (450 Cg−1 or 900 Fg−1) when compared with bare NiMoO4 nanoparticles (350 Cg−1 or 700 Fg−1) at the current density of 1 A g−1. Our findings show that the incorporation of rGO and NiMoO4 NP redox reactions with a porous structure can benefit the future development of supercapacitors.
Improvements of Motor Performances in the Drosophila LRRK2 Loss-of-Function Model of Parkinson’s Disease: Effects of Dialyzed Leucocyte Extracts from Human Serum
Authors: Diana Andrea , Collu Maria , Casu Maria Antonietta , Mocci Ignazia , Aguilar-Santelises Miguel , Setzu Maria Dolores
Published: January 2020

Within neurodegenerative syndromes, Parkinson’s disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, Drosophila melanogaster (D. melanogaster), with leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain, provides mechanistic insights into corresponding human behaviour, possibly disclosing some physiopathologic features of PD in both genetic and sporadic forms. Moreover, several data support the boosting impact of innate and adaptive immunity pathways for driving the progression of PD. In this context, human dialyzable leukocyte extracts (DLE) have been extensively used to transfer antigen-specific information that influences the activity of various immune components, including inflammatory cytokines. Hence, the main goal of our study was to ascertain the therapeutic potential of DLE from male and female donors on D. melanogaster LRRK2 loss-of-function, as compared to D. melanogaster wild-type (WT), in terms of rescuing physiological parameters, such as motor and climbing activities, which are severely compromised in the mutant flies. Finally, in search of the anatomical structures responsible for restored functions in parkinsonian-like mutant flies, we found a topographical correlation between improvement of locomotor performances and an increased number of dopaminergic neurons in selective areas of LRRK2 mutant brains.
On Assessing Driver Awareness of Situational Criticalities: Multi-modal Bio-Sensing and Vision-Based Analysis, Evaluations, and Insights
Authors: Siddharth Siddharth , Trivedi Mohan M.
Published: January 2020

Automobiles for our roadways are increasingly using advanced driver assistance systems. The adoption of such new technologies requires us to develop novel perception systems not only for accurately understanding the situational context of these vehicles, but also to infer the driver’s awareness in differentiating between safe and critical situations. This manuscript focuses on the specific problem of inferring driver awareness in the context of attention analysis and hazardous incident activity. Even after the development of wearable and compact multi-modal bio-sensing systems in recent years, their application in driver awareness context has been scarcely explored. The capability of simultaneously recording different kinds of bio-sensing data in addition to traditionally employed computer vision systems provides exciting opportunities to explore the limitations of these sensor modalities. In this work, we explore the applications of three different bio-sensing modalities namely electroencephalogram (EEG), photoplethysmogram (PPG) and galvanic skin response (GSR) along with a camera-based vision system in driver awareness context. We assess the information from these sensors independently and together using both signal processing- and deep learning-based tools. We show that our methods outperform previously reported studies to classify driver attention and detecting hazardous/non-hazardous situations for short time scales of two seconds. We use EEG and vision data for high resolution temporal classification (two seconds) while additionally also employing PPG and GSR over longer time periods. We evaluate our methods by collecting user data on twelve subjects for two real-world driving datasets among which one is publicly available (KITTI dataset) while the other was collected by us (LISA dataset) with the vehicle being driven in an autonomous mode. This work presents an exhaustive evaluation of multiple sensor modalities on two different datasets for attention monitoring and hazardous events classification.
Risk of Moisture in Diffusionally Open Roofs with Cross-Laminated Timber for Northern Coastal Climates
Authors: Sadłowska-Sałęga Agnieszka , Wąs Krzysztof
Published: January 2020

The paper is an attempt to answer the question whether the material-optimized roof construction using cross-laminated timber (CLT) is safe in terms of moisture content in the demanding northern costal climates. The proposed roof structure meets the strength requirements. The partition is diffusionally open, which facilitates moisture transport. However, there is a concern whether the applied layer system allows maintaining a safe level of moisture content below critical moisture content (CMC), which has been set at 20%. The article presents the annual hygrothermal calculation of the proposed roof slope for four locations of northern Europe and Greenland characterized by costal or subpolar climate. Four scenarios of indoor air relative humidity were considered: free floating, RHmin = 40%RH, RHmin = 50%, RHmin = 60%. In all cases, the minimum indoor temperature was 20 °C. The analysis was carried out using WUFI®Plus software. The calculation results showed that the moisture content did not exceed 20% in the CLT layer at any of the described locations. However, for the two coldest climates the assumed level of safety has been exceeded in the roof oriented strand board (OSB) sheathing.
Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells
Authors: Skoda Jan , Neradil Jakub , Staniczkova Zambo Iva , Nunukova Alena , Macsek Peter , Borankova Karolina , Dobrotkova Viera , Nemec Pavel , Sterba Jaroslav , Veselska Renata
Published: January 2020

Serial xenotransplantation of sorted cancer cells in immunodeficient mice remains the most complex test of cancer stem cell (CSC) phenotype. However, we have demonstrated in various sarcomas that putative CSC surface markers fail to identify CSCs, thereby impeding the isolation of CSCs for subsequent analyses. Here, we utilized serial xenotransplantation of unsorted rhabdomyosarcoma cells in NOD/SCID gamma (NSG) mice as a proof-of-principle platform to investigate the molecular signature of CSCs. Indeed, serial xenotransplantation steadily enriched for rhabdomyosarcoma stem-like cells characterized by enhanced aldehyde dehydrogenase activity and increased colony and sphere formation capacity in vitro. Although the expression of core pluripotency factors (SOX2, OCT4, NANOG) and common CSC markers (CD133, ABCG2, nestin) was maintained over the passages in mice, gene expression profiling revealed gradual changes in several stemness regulators and genes linked with undifferentiated myogenic precursors, e.g., SOX4, PAX3, MIR145, and CDH15. Moreover, we identified the induction of a hybrid epithelial/mesenchymal gene expression signature that was associated with the increase in CSC number. In total, 60 genes related to epithelial or mesenchymal traits were significantly altered upon serial xenotransplantation. In silico survival analysis based on the identified potential stemness-associated genes demonstrated that serial xenotransplantation of unsorted rhabdomyosarcoma cells in NSG mice might be a useful tool for the unbiased enrichment of CSCs and the identification of novel CSC-specific targets. Using this approach, we provide evidence for a recently proposed link between the hybrid epithelial/mesenchymal phenotype and cancer stemness.
Deep Sequencing Analysis Reveals Distinctive Non-Coding RNAs When Comparing Tumor Multidrug-Resistant Cells and Extracellular Vesicles with Drug-Sensitive Counterparts
Authors: Sousa Diana , Matthiesen Rune , Lima Raquel T. , Vasconcelos M. Helena
Published: January 2020

Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-efflux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, different studies have shown that extracellular vesicles (EVs) participate in the communication between MDR cells and drug-sensitive counterparts, promoting dissemination of the MDR phenotype. In the present work, we aimed to identify RNA species present in MDR cells and in EVs released by those cells, which may be associated with the MDR phenotype. The RNA content from two pairs (leukemia and lung cancer) of MDR (P-gp overexpressing) cells and their drug-sensitive counterparts, as well as from their EVs, was analyzed by deep sequencing. Our results showed distinctive transcripts for MDR cells and their EVs, when compared with their drug-sensitive counterparts. Remarkably, two pseudogenes (a novel pseudogene and RNA 5.8S ribosomal pseudogene 2) were found to be increased in EVs released by MDR cells in both leukemia and lung cancer models. Moreover, six miRs (miR-204-5p, miR-139-5p, miR-29c-5p, miR-551b-3p, miR-29b-2-5p, and miR-204-3p) exhibited altered levels in lung cancer MDR cells and their EVs. This study provides insights into the contribution of EVs to MDR.
Oncogenic Role of an Epigenetic Reader of m6A RNA Modification: YTHDF1 in Merkel Cell Carcinoma
Authors: Orouji Elias , Peitsch Wiebke K. , Orouji Azadeh , Houben Roland , Utikal Jochen
Published: January 2020

Merkel cell carcinoma is a deadly skin cancer, which in the majority of cases is caused by the Merkel cell polyomavirus (MCPyV). The viral small T antigen is regarded as the dominant oncoprotein expressed in the tumor cells. We used genomic screening of copy number aberrations along with transcriptomic analysis to investigate regions with amplification that harbor differentially expressed genes. We identified YTHDF1, a protein that is a reader of N6-methyladenosine (m6A) RNA modifications, to have high copy gains and to be highly expressed in Merkel cell carcinoma. Importantly, we identified the presence of m6A on small T antigen mRNA suggesting a relation between YTHDF1 amplification and MCPyV gene expression. Interestingly, knockdown of YTHDF1 in Merkel cell carcinoma (MCC) cell lines negatively affected the translation initiation factor eIF3 and reduced proliferation and clonogenic capacity in vitro. Furthermore, analysis of survival data revealed worse overall survival in YTHDF1high MCC patients compared to YTHDF1low patients. Our findings indicate a novel oncogenic role of YTHDF1 through m6A machinery in the tumorigenesis of MCC.
Selective Targeting of Cancer Stem Cells (CSCs) Based on Photodynamic Therapy (PDT) Penetration Depth Inhibits Colon Polyp Formation in Mice
Authors: Kim Jun Ki , Byun Mi Ran , Maeng Chi Hoon , Kim Yi Rang , Choi Jin Woo
Published: January 2020

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon; therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.
A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice
Authors: Sakai Yasuhiro , Rezano Andri , Okada Seiji , Ohtsuki Takahiro , Kawashima Yoshiaki , Tsukamoto Tetsuya , Suzuki Motoshi , Kohara Michinori , Takeya Motohiro , Sakaguchi Nobuo , Kuwahara Kazuhiko
Published: January 2020

Hodgkin lymphoma (HL) is one of the most difficult neoplasms in terms of cytopathological research owing to the lack of established cytological murine models. Although HL is believed to be of lymphoid germinal center B-cell origin, HL cells exhibit unique biphenotypic characteristics of B cells and macrophages. B-cell/macrophage biphenotypic cells have also been identified in the spleen of Lyn-deficient mice. Moreover, Lyn-targeting germinal center-associated nuclear protein (GANP)-transgenic mice (Ig-ganpTg mice) spontaneously develop a lymphoid tumor. We aimed to investigate whether the lymphoid tumor developed in Ig-ganpTg mice exhibit biphenotypic characteristics of B cells/macrophages that correspond to human HL. Here, we demonstrated GANP overexpression in human HL cells and found that it may regulate transdifferentiation between B cells and macrophages. We also demonstrated that tumors were comparable with B-cell/macrophage biphenotypic Hodgkinoid lymphomas. The tumor cells expressed macrophage-related F4/80, CD68, and CD204 as well as cytoplasmic B220 and µ-/κ-chains; in addition, these cells exhibited phagocytic activity. These cells also expressed transcripts of CD30; c-fms; and the cytokines monocyte chemoattractant protein (MCP)-1, MCP-5, RANTES, tumor necrosis factor-α and thrombopoietin associated with macrophages as well as granulocyte/macrophage colony-stimulating factor, interleukin (IL)-4, IL-10, IL-12, and IL-13. Ig-ganpTg mice represent a novel cytological model for the study of cytopathological etiology and oncogenesis of HL.
Ubiquitin-Specific Protease 21 Promotes Colorectal Cancer Metastasis by Acting as a Fra-1 Deubiquitinase
Authors: Yun Sun-Il , Hong Hye Kyung , Yeo So-Young , Kim Seok-Hyung , Cho Yong Beom , Kim Kyeong Kyu
Published: January 2020

Fos-related-antigen-1 (Fra-1), a member of the activator protein-1 (AP-1) transcription factor superfamily, has an essential role in cancer progress and metastasis and Fra-1 is considered a therapeutic target in metastatic cancer including metastatic colorectal cancer (mCRC). However, its regulation at protein level has not yet been clearly elucidated. We found that ubiquitin-specific protease 21 (USP21) increases Fra-1 stability by deubiquitinating Fra-1 and enhances the expression of Fra-1 target genes in colon cancer cells. We also showed that USP21 controlled Fra-1-dependent migration and invasion activities. The oncogenic property of USP21 was confirmed by a significant reduction in liver metastasis when USP21-knockdown cancer cells were injected intrasplenically into mice. Consistently, clinicopathological analysis of colorectal cancer patients revealed a correlation of USP21 expression with high-grade carcinoma and life span. These results demonstrate that USP21 enhances Fra-1 stability and AP-1 target gene expression by deubiquitinating Fra-1. Therefore, USP21 is considered an attractive therapeutic target in mCRC with high Fra-1 expression.
The EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas
Authors: Segura-Collar Berta , Gargini Ricardo , Tovar-Ambel Elena , Hernández-SanMiguel Esther , Epifano Carolina , Pérez de Castro Ignacio , Hernández-Laín Aurelio , Casas-Tintó Sergio , Sánchez-Gómez Pilar
Published: January 2020

Despite the high frequency of EGFR and TP53 genetic alterations in gliomas, little is known about their crosstalk during tumor progression. Here, we described a mutually exclusive distribution between mutations in these two genes. We found that wild-type p53 gliomas are more aggressive than their mutant counterparts, probably because the former accumulate amplifications and/or mutations in EGFR and show a stronger activation of this receptor. In addition, we identified a series of genes associated with vesicular trafficking of EGFR in p53 wild-type gliomas. Among these genes, TMEM167A showed the strongest implication in overall survival in this group of tumors. In agreement with this observation, inhibition of TMEM167A expression impaired the subcutaneous and the intracranial growth of wild-type p53 gliomas, regardless of the presence of EGFR mutations. In the absence of p53 mutations, TMEM167A knockdown reduced the acidification of intracellular vesicles, affecting the autophagy process and impairing EGFR trafficking and signaling. This effect was mimicked by an inhibitor of the vacuolar ATPase. We propose that the increased aggressiveness of wild-type p53 gliomas might be due to the increase in growth factor signaling activity, which depends on the regulation of vesicular trafficking by TMEM167A.
Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis
Authors: Skrzypek Klaudia , Majka Marcin
Published: January 2020

SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs.
Selective Hydrogenation of Acetylene Catalysed by a B12N12 Cluster Doped with a Single Nickel Atom: A DFT Study
Authors: Wang Yun , Kang Lihua
Published: January 2020

To obtain a catalyst based on a non-precious metal that can replace traditional palladium-based selective catalysts of acetylene hydrogenation, the catalytic performances of two different configurations of a B12N12 cluster doped with a single nickel atom were studied by a density functional theory computational approach. After analysing the effect that the adsorption of reactants onto the clusters has on the reaction path, we determined the lowest energy path for the acetylene double hydrogenation. Comparing the acetylene hydrogenation activities and ethylene product selectivities of the B11N12Ni and B12N11Ni clusters, which have different doping sites, we determined the activities of these two catalysts to be similar to each other; however, the B11N12Ni cluster was calculated to have higher selectivity for ethylene as a product. This difference may be related to the moderate adsorption of hydrogen and acetylene on the B11N12Ni cluster. As a new type of nickel-based single-atom catalyst, B11N12Ni clusters may have research value in the selective hydrogenation of acetylene.
Photodegradation of Gas Phase Benzene by SnO2 Nanoparticles by Direct Hole Oxidation Mechanism
Authors: Chen Shi , Sun Zhiguo , Zhang Li , Xie Hongyong
Published: January 2020

Photodegradation of gas phase benzene by SnO2 nanoparticles has been studied in humid air, dry air and N2 by using a tubular photoreactor. The SnO2 nanoparticles are synthesized by the oxidation of anhydrous stannic chloride (SnCl4) in a propane/air turbulent flame. Direct hole oxidation and the ·OH radical mechanisms have been discussed based on experimental results. The goal of this research is to explore a viable and efficient alternative photocatalyst and photocatalytic process, in particular, for humidity-tolerant photocatalyst or photocatalytic process in environmental applications.
Characterization and Comparative Performance of TiO2 Photocatalysts on 6-Mercaptopurine Degradation by Solar Heterogeneous Photocatalysis
Authors: González-Burciaga Luis A. , Núñez-Núñez Cynthia M. , Morones-Esquivel Miriam M. , Avila-Santos Manuel , Lemus-Santana Adela , Proal-Nájera José B.
Published: January 2020

The crystallographic properties of two titanium dioxide (TiO2) photocatalysts, P25, and commercial C1-TiO2 reactive grade, were analyzed by X-ray diffraction (XRD) and the band-gap was calculated with UV–Vis spectrometry with integration sphere. Then, their performance was tested in the degradation of 6-mercaptopurine (6-MP) by heterogeneous photocatalysis with solar radiation under different pH conditions and the addition of hydrogen peroxide (H2O2); the degradation efficiency was monitored by UV–Vis spectrophotometry. The XRD analysis showed that both photocatalysts studied have anatase phase, while only P25 contains rutile; the band gap values were lower, in both catalysts, than those reported for catalysts obtained by the sol-gel method. With both photocatalysts, degradation experiments showed efficiency greater than 98% in experiments in the presence of H2O2 regardless of pH. The properties of the photocatalysts, along with the data obtained from the experimentation, helped determine the best semiconductor for the degradation of 6-MP with these operating conditions in this work.
Potential Cycling Effects on Activities of Nickel-Mediated Benzyl Alcohol and Glycine Electrooxidation in Alkaline Solutions
Authors: Wei Yuyang , Zhang Wenbin
Published: January 2020

Nickel electrodes under continuous potential cycling were applied for the electrooxidation of benzyl alcohol and glycine in KOH solutions, and their activities were measured and compared by cyclic voltammetry. It is shown that intrinsic activities of both reactions decrease with the increasing catalyst loadings, and a more significant decreasing trend was observed in glycine electrooxidation when compared to benzyl alcohol electrooxidation. These phenomena may be explained by an increasing of mass loading induced a decrease of the catalyst surface conductivity, structure changes of Ni(OH)2 from α-phase to β-phase, and the intercalation of glycine molecules into nickel hydroxide interlayers.
Glutamine Synthetase 1 Increases Autophagy Lysosomal Degradation of Mutant Huntingtin Aggregates in Neurons, Ameliorating Motility in a Drosophila Model for Huntington’s Disease
Authors: Vernizzi Luisa , Paiardi Chiara , Licata Giusimaria , Vitali Teresa , Santarelli Stefania , Raneli Martino , Manelli Vera , Rizzetto Manuela , Gioria Mariarosa , Pasini Maria E. , Grifoni Daniela , Vanoni Maria A. , Gellera Cinzia , Taroni Franco , Bellosta Paola
Published: January 2020

Glutamine Synthetase 1 (GS1) is a key enzyme that catalyzes the ATP-dependent synthesis of l-glutamine from l-glutamate and is also member of the Glutamate Glutamine Cycle, a complex physiological process between glia and neurons that controls glutamate homeostasis and is often found compromised in neurodegenerative diseases including Huntington’s disease (HD). Here we report that the expression of GS1 in neurons ameliorates the motility defects induced by the expression of the mutant Htt, using a Drosophila model for HD. This phenotype is associated with the ability of GS1 to favor the autophagy that we associate with the presence of reduced Htt toxic protein aggregates in neurons expressing mutant Htt. Expression of GS1 prevents the TOR activation and phosphorylation of S6K, a mechanism that we associate with the reduced levels of essential amino acids, particularly of arginine and asparagine important for TOR activation. This study reveals a novel function for GS1 to ameliorate neuronal survival by changing amino acids’ levels that induce a “starvation-like” condition responsible to induce autophagy. The identification of novel targets that inhibit TOR in neurons is of particular interest for the beneficial role that autophagy has in preserving physiological neuronal health and in the mechanisms that eliminate the formation of toxic aggregates in proteinopathies.
Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing
Authors: Maidarti Mila , Anderson Richard A. , Telfer Evelyn E.
Published: January 2020

The preservation of genome integrity in the mammalian female germline from primordial follicle arrest to activation of growth to oocyte maturation is fundamental to ensure reproductive success. As oocytes are formed before birth and may remain dormant for many years, it is essential that defence mechanisms are monitored and well maintained. The phosphatase and tensin homolog of chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, Akt) is a major signalling pathway governing primordial follicle recruitment and growth. This pathway also contributes to cell growth, survival and metabolism, and to the maintenance of genomic integrity. Accelerated primordial follicle activation through this pathway may result in a compromised DNA damage response (DDR). Additionally, the distinct DDR mechanisms in oocytes may become less efficient with ageing. This review considers DNA damage surveillance mechanisms and their links to the PTEN/PI3K/Akt signalling pathway, impacting on the DDR during growth activation of primordial follicles, and in ovarian ageing. Targeting DDR mechanisms within oocytes may be of value in developing techniques to protect ovaries against chemotherapy and in advancing clinical approaches to regulate primordial follicle activation.
Direct Activation of TRPC3 Channels by the Antimalarial Agent Artemisinin
Authors: Urban Nicole , Schaefer Michael
Published: January 2020

(1) Background: Members of the TRPC3/TRPC6/TRPC7 subfamily of canonical transient receptor potential (TRP) channels share an amino acid similarity of more than 80% and can form heteromeric channel complexes. They are directly gated by diacylglycerols in a protein kinase C-independent manner. To assess TRPC3 channel functions without concomitant protein kinase C activation, direct activators are highly desirable. (2) Methods: By screening 2000 bioactive compounds in a Ca2+ influx assay, we identified artemisinin as a TRPC3 activator. Validation and characterization of the hit was performed by applying fluorometric Ca2+ influx assays and electrophysiological patch-clamp experiments in heterologously or endogenously TRPC3-expressing cells. (3) Results: Artemisinin elicited Ca2+ entry through TRPC3 or heteromeric TRPC3:TRPC6 channels, but did not or only weakly activated TRPC6 and TRPC7. Electrophysiological recordings confirmed the reversible and repeatable TRPC3 activation by artemisinin that was inhibited by established TRPC3 channel blockers. Rectification properties and reversal potentials were similar to those observed after stimulation with a diacylglycerol mimic, indicating that artemisinin induces a similar active state as the physiological activator. In rat pheochromocytoma PC12 cells that endogenously express TRPC3, artemisinin induced a Ca2+ influx and TRPC3-like currents. (4) Conclusions: Our findings identify artemisinin as a new biologically active entity to activate recombinant or native TRPC3-bearing channel complexes in a membrane-confined fashion.
The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy
Authors: Michie Jessica , Kearney Conor J. , Hawkins Edwin D. , Silke John , Oliaro Jane
Published: January 2020

One of the hallmarks of cancer cells is their ability to evade cell death via apoptosis. The inhibitor of apoptosis proteins (IAPs) are a family of proteins that act to promote cell survival. For this reason, upregulation of IAPs is associated with a number of cancer types as a mechanism of resistance to cell death and chemotherapy. As such, IAPs are considered a promising therapeutic target for cancer treatment, based on the role of IAPs in resistance to apoptosis, tumour progression and poor patient prognosis. The mitochondrial protein smac (second mitochondrial activator of caspases), is an endogenous inhibitor of IAPs, and several small molecule mimetics of smac (smac-mimetics) have been developed in order to antagonise IAPs in cancer cells and restore sensitivity to apoptotic stimuli. However, recent studies have revealed that smac-mimetics have broader effects than was first attributed. It is now understood that they are key regulators of innate immune signalling and have wide reaching immuno-modulatory properties. As such, they are ideal candidates for immunotherapy combinations. Pre-clinically, successful combination therapies incorporating smac-mimetics and oncolytic viruses, as with chimeric antigen receptor (CAR) T cell therapy, have been reported, and clinical trials incorporating smac-mimetics and immune checkpoint blockade are ongoing. Here, the potential of IAP antagonism to enhance immunotherapy strategies for the treatment of cancer will be discussed.
Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice
Authors: Di Emidio Giovanna , Placidi Martina , Rea Francesco , Rossi Giulia , Falone Stefano , Cristiano Loredana , Nottola Stefania , D’Alessandro Anna Maria , Amicarelli Fernanda , Palmerini Maria Grazia , Tatone Carla
Published: January 2020

Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1α), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response.