bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources and Characteristics of Particulate Matter in Subway Tunnels in Seoul, Korea
Authors: Lee Yongil , Lee Young-Chul , Kim Taesung , Choi Jin Seok , Park Duckshin
Published: November 2018

Hazards related to particulate matter (PM) in subway systems necessitate improvement of the air quality. As a first step toward establishing a management strategy, we assessed the physicochemical characteristics of PM in a subway system in Seoul, South Korea. The mean mass of PM10 and PM2.5 concentrations (n = 13) were 213.7 ± 50.4 and 78.4 ± 8.8 µg/m3, with 86.0% and 85.9% of mass concentration. Chemical analysis using a thermal–optical elemental/organic carbon (EC–OC) analyzer, ion chromatography (IC), and inductively coupled plasma (ICP) spectroscopy indicated that the chemical components in the subway tunnel comprised 86.0% and 85.9% mass concentration of PM10 and PM2.5. Fe was the most abundant element in subway tunnels, accounting for higher proportions of PM, and was detected in PM with diameters >94 nm. Fe was present mostly as iron oxides, which were emitted from the wheel–rail–brake and pantograph–catenary wire interfaces. Copper particles were 96–150 nm in diameter and were likely emitted via catenary wire arc discharges. Furthermore, X-ray diffraction analysis (XRD) showed that the PM in subway tunnels was composed of calcium carbonate (CaCO3), quartz (SiO2), and iron oxides (hematite (α-Fe2O3) and maghemite-C (γ-Fe2O3)). Transmission electron microscopy images revealed that the PM in subway tunnels existed as agglomerates of iron oxide particle clusters a few nanometers in diameter, which were presumably generated at the aforementioned interfaces and subsequently attached onto other PM, enabling the growth of aggregates. Our results can help inform the management of PM sources from subway operation.
The Efficacy of the Tabby Improved Prevention and Intervention Program in Reducing Cyberbullying and Cybervictimization among Students
Authors: Sorrentino Anna , Baldry Anna Costanza , Farrington David P.
Published: November 2018

Background. This article presents results from the evaluation of the Tabby Improved Prevention and Intervention Program (TIPIP) for cyberbullying and cybervictimization. TIPIP is theoretically designed to address cyberbullying and cybervictimization. It is the first program in this field developed combining the Ecological System Theory and the Threat Assessment Approach. Method. The Tabby Improved program was evaluated using an experimental design with 759 Italian students (aged 10–17 years) randomly allocated via their classes to either the Experimental or Control Group. Results. Repeated measures ANOVAs showed a significant decrease both in cyberbullying and cybervictimization among students who received the intervention with a follow-up period of six months. The program was more effective for boys than for girls. Conclusions. Because cyberbullying is a cruel problem negatively affecting those involved, validated interventions that prove their efficacy in reducing the problem using experimental designs should be widely tested and promoted, paying particular attention to implementing a program fully to increase and guarantee its effectiveness.
Evaluation and Prediction of the Ecological Footprint and Ecological Carrying Capacity for Yangtze River Urban Agglomeration Based on the Grey Model
Authors: Peng Benhong , Wang Yuanyuan , Elahi Ehsan , Wei Guo
Published: November 2018

The conflict between economic development and environmental protection has become increasingly prominent in the urbanization process of the Yangtze River urban agglomeration, the most economically developed region in Jiangsu Province in China. In order to investigate the sustainable development status, and thus provide decision support for the sustainable development of this region, the ecological footprint model was utilized to evaluate and analyze the ecological footprint per capita, the ecological carrying capacity per capita, and the ecological deficit per capita for the period from 2013 to 2017. Furthermore, the Grey model is employed to predict the development trend of the ecological footprint for 2018 to 2022. The evaluation results show that the ecological footprint per capita has been increasing year by year since 2013, reaching a peak of 2.3897 hm2 in 2015 before declining again. In the same period, the available ecological carrying capacity per capita and the ecological footprint per capita basically developed in the same direction, resulting in an ecological deficit per capita and gradually increasing from 2013 to a peak of 2.0303 hm2 in 2015 before declining. It is also found that the change of ecological carrying capacity is not substantial, and the change of the ecological deficit is mainly caused by a huge change of the ecological footprint. The forecast results show that the ecological deficit per capita will reach 1.1713 hm2 in 2018, which will be another deficit peak after 2015. However, in the later period until 2022, the ecological deficit per capita will begin to decline year by year. These results can provide effective inspirations for reducing the ecological deficit of the Yangtze River urban agglomeration, thus promoting the coordinated development of the economy and environment in this area.
“In my day…”- Parents’ Views on Children’s Physical Activity and Screen Viewing in Relation to Their Own Childhood
Authors: Solomon-Moore Emma , Emm-Collison Lydia G. , Sebire Simon J. , Toumpakari Zoi , Thompson Janice L. , Lawlor Deborah A. , Jago Russell
Published: November 2018

Physical activity and screen viewing are associated with cardio-metabolic risk factors, psychological wellbeing, and academic performance among children. Across the last generation, children’s physical activity and screen viewing behaviours have changed, coinciding with changes to the home and neighbourhood environment. This study aimed to qualitatively explore parents’ views on their 8–9-year-old child’s childhood and how this compares to experiences from their own childhood, with a specific focus on physical activity and screen viewing behaviours. Semi-structured telephone interviews were conducted with 51 parents (mean age = 41.2 years, range 31.5 to 51.5 years), between July and October 2016. Inductive and deductive content analyses were used to explore parents’ perceptions of their child’s physical activity and screen viewing behaviours in comparison to their own childhood behaviours. Interview data revealed that compared to the relative freedom they recalled as children, parents restrict their children’s independent mobility and outdoor play due to concerns about safety. Despite their children having greater access to structured activities than they did as children, parents feel their children are “missing out,” and perceived their own childhood as better with regards to maximising independent and outdoor play and limiting screen viewing. Innovative strategies are needed to change the social norms surrounding children’s independent mobility and outdoor play.
Impact of Drinking Water Quality on the Development of Enteroviral Diseases in Korea
Authors: Joshi Yadav P. , Kim Jong-Hun , Kim Ho , Cheong Hae-Kwan
Published: November 2018

Enterovirus diseases are fecal-orally transmitted, and its transmission may be closely related with the drinking water quality and other environmental factors. This study aimed to assess the association between environmental factors including drinking water quality and the incidence of enteroviral diseases in metropolitan provinces of Korea. Using monthly number of hand-foot-mouth disease (HFMD), aseptic meningitis (AM) and acute hemorrhage conjunctivitis (AHC) cases, generalized linear Poisson model was applied to estimate the effects of environmental factors on the monthly cases. An increase of mean temperature was associated with an increase of enteroviral diseases at 0–2 months lag, while an increase of turbidity was associated with increase in HFMD at 1 month lag and a decrease in AHC. An increase of residual chlorine in municipal drinking water was associated with a decrease in HFMD and AHC 2 and 3 months later. An increase of pH was associated with a maximum increase in AM 3 months later. The meta-analysis revealed the effects of the provincial and pooled variation in percent change of risks of environmental factors on HFMD, AM, and AHC cases at specific selected lags. This study suggests that the drinking water quality is one of the major determinants on enteroviral diseases.
Parenting Practices as a Mediator in the Association Between Family Socio-Economic Status and Screen-Time in Primary Schoolchildren: A Feel4Diabetes Study
Authors: De Lepeleere Sara , De Bourdeaudhuij Ilse , Van Stappen Vicky , Huys Nele , Latomme Julie , Androutsos Odysseas , Manios Yannis , Cardon Greet , Verloigne Maïté
Published: November 2018

The aim of this study was to examine the mediating effects of specific parenting practices on the association between family socio-economic status (SES) and screen-time of 6- to 9-year-old children from families with an increased risk of developing type 2 diabetes. This cross-sectional study, focusing on families with an increased risk of developing type 2 diabetes, used the Belgian baseline data of the Movie Models intervention, integrated within the European Feel4Diabetes intervention, and included 247 parents (57.6% lower SES family; 78.0% mothers) who completed a questionnaire. Mediating effects were tested using MacKinnon’s product-of-coefficients test via multilevel linear regression analyses. Being consistent concerning rules about gaming (β = 0.127; standard error = 0.055; 95% CI = 0.020; 0.234) and avoiding negative role modeling concerning TV-time (β = −0.082; standard error = 0.040; 95% CI = −0.161; −0.003) significantly mediated the inverse association between family SES and children’s screen-time. Parents from lower SES families were more consistent concerning rules about gaming and watched more TV nearby their child compared to parents from higher SES families, and these parenting practices were related to more screen-time. No other parenting practices were found to mediate this association. Thus, parents from lower SES families with a higher risk for developing type 2 diabetes might limit their own TV-time nearby their child to reduce their child’s screen-time. Future research should examine other possible mediating factors to develop effective interventions targeting this important at-risk group.
Fear of Terror and Psychological Well-Being: The Moderating Role of Emotional Intelligence
Authors: Asad Ali Shah Syed , Yezhuang Tian , Muhammad Shah Adnan , Khan Durrani Dilawar , Jamal Shah Syed
Published: November 2018

The purpose of this study was to empirically explore whether or not the level of emotional intelligence of adolescents mitigates the potential adverse effects of the fear of terror on their psychological well-being. Data for this study were collected through a voluntary survey from a sample of 385 adolescents residing in the terrorism-affected provinces of Pakistan: Khyber Pakhtunkhwa (KPK) and Balochistan. The results from the structural equation modeling revealed that fear of terrorism had a significant negative relationship with the psychological well-being of adolescents. The study results further revealed that emotional intelligence significantly moderated the relationship between the fear of terrorism and the psychological well-being of the adolescents. Therefore, the negative relationship was stronger for those with low emotional intelligence and weaker for those with high emotional intelligence. This study also discusses several practical implications along with suggestions for future research.
Study on the Preferred Application-Oriented Index for Mental Fatigue Detection
Authors: Duan Tianhong , Zhang Nong , Li Kaiway , Hou Xuelin , Pei Jun
Published: November 2018

Most of the research on mental fatigue evaluation has mainly concentrated on some indexes that require sophisticated and large instruments that make the detection of mental fatigue cumbersome, time-consuming, and difficult to apply on a large scale. A quick and sensitive mental fatigue detection index is necessary so that mentally fatigued workers can be alerted in time and take corresponding countermeasures. However, to date, no studies have compared the sensitivity of common objective evaluation indexes. To solve these problems, this study recruited 56 human subjects. These subjects were evaluated using six fatigue indexes: the Stanford sleepiness scale, digital span, digital decoding, short-term memory, critical flicker fusion frequency (CFF), and speed perception deviation. The results of the fatigue tests before and after mental fatigue were compared, and a one-way analysis of variance (ANOVA) was performed on the speed perception deviation. The results indicated the significance of this index. Considering individual differences, the relative fatigue index (RFI) was proposed to compare the sensitivity of the indexes. The results showed that when the self-rated fatigue grade changed from non-fatigue to mild fatigue, the ranges of RFI values for digital span, digital decoding, short-term memory, and CFF were 0.175–0.258, 0.194–0.316, 0.068–0.139, and 0.055–0.075, respectively. Correspondingly, when the self-rated fatigue grade changed to severe fatigue, the ranges of RFI values for the above indexes were 0.415–0.577, 0.482–0.669, 0.329–0.396, and 0.114–0.218, respectively. These results suggest that the sensitivity of the digital decoding, digital span, short-term memory, and CFF decreased sequentially when the self-evaluated fatigue grade changed from no fatigue to mild or severe fatigue. The RFI individuality of the speed perception deviation is highly variable and is not suitable as an evaluation index. In mental fatigue testing, digital decoding testing can provide faster, more convenient, and more accurate results.
Change Detection in Coral Reef Environment Using High-Resolution Images: Comparison of Object-Based and Pixel-Based Paradigms
Authors: Zhou Zhenjin , Ma Lei , Fu Tengyu , Zhang Ge , Yao Mengru , Li Manchun
Published: November 2018

Despite increases in the spatial resolution of satellite imagery prompting interest in object-based image analysis, few studies have used object-based methods for monitoring changes in coral reefs. This study proposes a high accuracy object-based change detection (OBCD) method intended for coral reef environment, which uses QuickBird and WorldView-2 images. The proposed methodological framework includes image fusion, multi-temporal image segmentation, image differencing, random forests models, and object-area-based accuracy assessment. For validation, we applied the method to images of four coral reef study sites in the South China Sea. We compared the proposed OBCD method with a conventional pixel-based change detection (PBCD) method by implementing both methods under the same conditions. The average overall accuracy of OBCD exceeded 90%, which was approximately 20% higher than PBCD. The OBCD method was free from salt-and-pepper effects and was less prone to images misregistration in terms of change detection accuracy and mapping results. The object-area-based accuracy assessment reached a higher overall accuracy and per-class accuracy than the object-number-based and pixel-number-based accuracy assessment.
Species-Level Vegetation Mapping in a Himalayan Treeline Ecotone Using Unmanned Aerial System (UAS) Imagery
Authors: Mishra Niti B. , Mainali Kumar P. , Shrestha Bharat B. , Radenz Jackson , Karki Debendra
Published: November 2018

Understanding ecological patterns and response to climate change requires unbiased data on species distribution. This can be challenging, especially in biodiverse but extreme environments like the Himalaya. This study presents the results of the first ever application of Unmanned Aerial Systems (UAS) imagery for species-level mapping of vegetation in the Himalaya following a hierarchical Geographic Object Based Image Analysis (GEOBIA) method. The first level of classification separated green vegetated objects from the rest with overall accuracy of 95%. At the second level, seven cover types were identified (including four woody vegetation species). For this, the suitability of various spectral, shape and textural features were tested for classifying them using an ensemble decision tree algorithm. Spectral features alone yielded ~70% accuracy (kappa 0.66) whereas adding textural and shape features marginally improved the accuracy (73%) but at the cost of a substantial increase in processing time. Contrast in plant morphological traits was the key to distinguishing nearby stands as different species. Hence, broad-leaved versus fine needle leaved vegetation were mapped more accurately than structurally similar classes such as Rhododendron anthopogon versus non-photosynthetic vegetation. Results highlight the potential and limitations of the suggested UAS-GEOBIA approach for detailed mapping of plant communities and suggests future research directions.
Immunohistochemical Evaluation of Aquaporin-4 and its Correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 Expressions in Fatal Traumatic Brain Injury
Authors: Neri Margherita , Frati Alessandro , Turillazzi Emanuela , Cantatore Santina , Cipolloni Luigi , Di Paolo Marco , Frati Paola , La Russa Raffaele , Maiese Aniello , Scopetti Matteo , Santurro Alessandro , Sessa Francesco , Zamparese Rosanna , Fineschi Vittorio
Published: November 2018

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance.
NVP-BEZ235 Attenuated Cell Proliferation and Migration in the Squamous Cell Carcinoma of Oral Cavities and p70S6K Inhibition Mimics its Effect
Authors: Hsu Cheng-Ming , Lin Pai-Mei , Lin Hsin-Ching , Tsai Yao-Te , Tsai Ming-Shao , Li Shau-Hsuan , Wu Ching-Yuan , Yang Yao-Hsu , Lin Sheng-Fung , Yang Ming-Yu
Published: November 2018

NVP-BEZ235 or BEZ235 is a dual inhibitor of adenosine triphosphate (ATP)-competitive phosphoinositide 3-kinase (PI3K)/mammalian-target-of-rapamycin (mTOR) and is promising for cancer treatment. Because it targets more than one downstream effector, a dual approach is promising for cancer treatment. The aim of this study was to evaluate the efficacy of NVP-BEZ235 in treating oral cavity squamous cell carcinoma (OSCC). Two human OSCC cell lines, SCC-4 and SCC-25, were used in this study. PI3K-AKT signaling, proliferation, and cell migratory and invasion capabilities of OSCC cells were examined. In NVP-BEZ235-treated SCC-4 and SCC-25 cells, the phosphorylation of 70-kDa ribosomal S6 kinase (p70S6K), but not mTOR, decreased within 24 h. NVP-BEZ235 inhibited OSCC-cell proliferation, migration, and invasion possibly by directly deregulating the phosphorylation of p70S6K. The phospho-p70S6K inhibitor mimicked the effects of NVP-BEZ235 for preventing proliferation and weakening the migratory and invasion abilities of SCC-4 and SCC-25 cells. This study further confirmed the effect of NVP-BEZ235 on OSCC cells and provided a new strategy for controlling the proliferation, migration, and invasion of OSCC cells using the phopho-p70S6K inhibitor.
Interferons and Dry Eye in Sjögren’s Syndrome
Authors: Ogawa Yoko , Shimizu Eisuke , Tsubota Kazuo
Published: November 2018

Various cytokines, including interferon (IFN)-γ and IL-17, are augmented, and autoreactive T cells and B cells are activated in the immune pathogenesis of Sjögren’s syndrome (SS). In particular, IFNs are involved in both the early stages of innate immunity by high level of type I IFN in glandular tissue and sera and the later stages of disease progression by type I and type II IFN producing T cells and B cells through B cell activating factor in SS. Genetically modified mouse models for some of these molecules have been reported and will be discussed in this review. New findings from human SS and animal models of SS have elucidated some of the mechanisms underlying SS-related dry eye. We will discuss IFN-γ and several other molecules that represent candidate targets for treating inflammation in SS-related dry eye.
Cellular and Molecular Events in the Airway Epithelium Defining the Interaction Between House Dust Mite Group 1 Allergens and Innate Defences
Authors: Zhang Jihui , Chen Jie , Robinson Clive
Published: November 2018

Serodominant group 1 allergens of house dust mites (HDMs) are cysteine protease digestive enzymes. By increasing the detection of any allergen by dendritic antigen presenting cells, upregulating inflammatory signalling molecules, and activating cells crucial to the transition from innate to acquired immune responses, the proteolytic activity of these HDM allergens also underlies their behaviour as inhalant allergens. The significance of this property is underlined by the attenuation of allergic responses to HDMs by novel inhibitors in experimental models. The group 1 HDM allergens act as prothrombinases, enabling them to operate the canonical stimulation of protease activated receptors 1 and 4. This leads to the ligation of Toll-like receptor 4, which is an indispensable component in HDM allergy development, and reactive oxidant-regulated gene expression. Intermediate steps involve epidermal growth factor receptor ligation, activation of a disintegrin and metalloproteases, and the opening of pannexons. Elements of this transduction pathway are shared with downstream signalling from biosensors which bind viral RNA, suggesting a mechanistic linkage between allergens and respiratory viruses in disease exacerbations. This review describes recent progress in the characterisation of an arterial route which links innate responses to inhaled allergens to events underpinning the progression of allergy to unrelated allergens.
Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells
Authors: Mungo Eleonora , Bergandi Loredana , Salaroglio Iris Chiara , Doublier Sophie
Published: November 2018

Emerging evidence supports the idea that a dysfunction in cell metabolism could sustain a resistant phenotype in cancer cells. As the success of chemotherapeutic agents is often questioned by the occurrence of multidrug resistance (MDR), a multiple cross-resistance towards different anti-cancer drugs represent a major obstacle to cancer treatment. The present study has clarified the involvement of the carbon metabolites in a more aggressive tumor colon adenocarcinoma phenotype and in a chemoresistant mesothelioma, and the role of pyruvate treatment in the reversion of the potentially related resistance. For the first time, we have shown that human colon adenocarcinoma cells (HT29) and its chemoresistant counterpart (HT29-dx) displayed different carbon metabolism: HT29-dx cells had a higher glucose consumption compared to HT29 cells, whereas human malignant mesothelioma (HMM) cells showed a lower glucose consumption compared to HT29 cells, accompanied by a lower pyruvate production and, consequently, a higher production of lactate. When treated with pyruvate, both HT29-dx and HMM cells exhibited a re-established accumulation of doxorubicin and a lower survival ability, a decreased activity of multidrug resistance protein 1 (MRP1) and a restored mitochondrial respiratory chain function, improving the effectiveness of the chemotherapeutic agents in these resistant cancer cells.
One Major Challenge of Sequencing Large Plant Genomes Is to Know How Big They Really Are
Authors: Doležel Jaroslav , Čížková Jana , Šimková Hana , Bartoš Jan
Published: November 2018

Any project seeking to deliver a plant or animal reference genome sequence must address the question as to the completeness of the assembly. Given the complexity introduced particularly by the presence of sequence redundancy, a problem which is especially acute in polyploid genomes, this question is not an easy one to answer. One approach is to use the sequence data, along with the appropriate computational tools, the other is to compare the estimate of genome size with an experimentally measured mass of nuclear DNA. The latter requires a reference standard in order to provide a robust relationship between the two independent measurements of genome size. Here, the proposal is to choose the human male leucocyte genome for this standard: its 1C DNA amount (the amount of DNA contained within unreplicated haploid chromosome set) of 3.50 pg is equivalent to a genome length of 3.423 Gbp, a size which is just 5% longer than predicted by the most current human genome assembly. Adopting this standard, this paper assesses the completeness of the reference genome assemblies of the leading cereal crops species wheat, barley and rye.
Identification of Potential Key Genes Associated with Adipogenesis through Integrated Analysis of Five Mouse Transcriptome Datasets
Authors: Zhang Song , Wang Li , Li Shijun , Zhang Wenzhen , Ma Xueyao , Cheng Gong , Yang Wucai , Zan Linsen
Published: November 2018

Adipose tissue is the most important energy metabolism and secretion organ, and these functions are conferred during the adipogenesis process. However, the cause and the molecular events underlying adipogenesis are still unclear. In this study, we performed integrated bioinformatics analyses to identify vital genes involved in adipogenesis and reveal potential molecular mechanisms. Five mouse high-throughput expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database; these datasets contained 24 samples of 3T3-L1 cells during adipogenesis, including 12 undifferentiated samples and 12 differentiated samples. The five datasets were reanalyzed and integrated to select differentially expressed genes (DEGs) during adipogenesis via the robust rank aggregation (RRA) method. Functional annotation of these DEGs and mining of key genes were then performed. We also verified the expression levels of some potential key genes during adipogenesis. A total of 386 consistent DEGs were identified, with 230 upregulated genes and 156 downregulated genes. Gene Ontology (GO) analysis showed that the biological functions of the DEGs primarily included fat cell differentiation, lipid metabolic processes, and cell adhesion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly associated with metabolic pathways, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, the tumor necrosis factor (TNF) signaling pathway, and the FoxO signaling pathway. The 30 most closely related genes among the DEGs were identified from the protein–protein interaction (PPI) network and verified by real-time quantification during 3T3-L1 preadipocyte differentiation. In conclusion, we obtained a list of consistent DEGs during adipogenesis through integrated analysis, which may offer potential targets for the regulation of adipogenesis and treatment of adipose dysfunction.
AMP-Activated Protein Kinase as a Key Trigger for the Disuse-Induced Skeletal Muscle Remodeling
Authors: Vilchinskaya Natalia A. , Krivoi Igor I. , Shenkman Boris S.
Published: November 2018

Molecular mechanisms that trigger disuse-induced postural muscle atrophy as well as myosin phenotype transformations are poorly studied. This review will summarize the impact of 5′ adenosine monophosphate -activated protein kinase (AMPK) activity on mammalian target of rapamycin complex 1 (mTORC1)-signaling, nuclear-cytoplasmic traffic of class IIa histone deacetylases (HDAC), and myosin heavy chain gene expression in mammalian postural muscles (mainly, soleus muscle) under disuse conditions, i.e., withdrawal of weight-bearing from ankle extensors. Based on the current literature and the authors’ own experimental data, the present review points out that AMPK plays a key role in the regulation of signaling pathways that determine metabolic, structural, and functional alternations in skeletal muscle fibers under disuse.
Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity
Authors: Liao Chengzhu , Li Yuchao , Tjong Sie Chin
Published: November 2018

Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their exceptionally high mechanical stiffness and strength, excellent electrical conductivity, high optical transparency, and good biocompatibility. In this article, we reviewed several techniques that are available for the synthesis of graphene-based nanomaterials, and discussed the biocompatibility and toxicity of such nanomaterials upon exposure to mammalian cells under in vitro and in vivo conditions. Various synthesis strategies have been developed for their fabrication, generating graphene nanomaterials with different chemical and physical properties. As such, their interactions with cells and organs are altered accordingly. Conflicting results relating biocompatibility and cytotoxicity induced by graphene nanomaterials have been reported in the literature. In particular, graphene nanomaterials that are used for in vitro cell culture and in vivo animal models may contain toxic chemical residuals, thereby interfering graphene-cell interactions and complicating interpretation of experimental results. Synthesized techniques, such as liquid phase exfoliation and wet chemical oxidation, often required toxic organic solvents, surfactants, strong acids, and oxidants for exfoliating graphite flakes. Those organic molecules and inorganic impurities that are retained in final graphene products can interact with biological cells and tissues, inducing toxicity or causing cell death eventually. The residual contaminants can cause a higher risk of graphene-induced toxicity in biological cells. This adverse effect may be partly responsible for the discrepancies between various studies in the literature.
Relative Contribution of PIN-Containing Secretory Vesicles and Plasma Membrane PINs to the Directed Auxin Transport: Theoretical Estimation
Authors: Hille Sander , Akhmanova Maria , Glanc Matouš , Johnson Alexander , Friml Jiří
Published: November 2018

The intercellular transport of auxin is driven by PIN-formed (PIN) auxin efflux carriers. PINs are localized at the plasma membrane (PM) and on constitutively recycling endomembrane vesicles. Therefore, PINs can mediate auxin transport either by direct translocation across the PM or by pumping auxin into secretory vesicles (SVs), leading to its secretory release upon fusion with the PM. Which of these two mechanisms dominates is a matter of debate. Here, we addressed the issue with a mathematical modeling approach. We demonstrate that the efficiency of secretory transport depends on SV size, half-life of PINs on the PM, pH, exocytosis frequency and PIN density. 3D structured illumination microscopy (SIM) was used to determine PIN density on the PM. Combining this data with published values of the other parameters, we show that the transport activity of PINs in SVs would have to be at least 1000× greater than on the PM in order to produce a comparable macroscopic auxin transport. If both transport mechanisms operated simultaneously and PINs were equally active on SVs and PM, the contribution of secretion to the total auxin flux would be negligible. In conclusion, while secretory vesicle-mediated transport of auxin is an intriguing and theoretically possible model, it is unlikely to be a major mechanism of auxin transport in planta.
Targeting Cancer with Phytochemicals via Their Fine Tuning of the Cell Survival Signaling Pathways
Authors: Chirumbolo Salvatore , Bjørklund Geir , Lysiuk Roman , Vella Antonio , Lenchyk Larysa , Upyr Taras
Published: November 2018

The role of phytochemicals as potential prodrugs or therapeutic substances against tumors has come in the spotlight in the very recent years, thanks to the huge mass of encouraging and promising results of the in vitro activity of many phenolic compounds from plant raw extracts against many cancer cell lines. Little but important evidence can be retrieved from the clinical and nutritional scientific literature, where flavonoids are investigated as major pro-apoptotic and anti-metastatic compounds. However, the actual role of these compounds in cancer is still far to be fully elucidated. Many of these phytochemicals act in a pleiotropic and poorly specific manner, but, more importantly, they are able to tune the reactive oxygen species (ROS) signaling to activate a survival or a pro-autophagic and pro-apoptosis mechanism, depending on the oxidative stress-responsive endowment of the targeted cell. This review will try to focus on this issue.
What Is the Evidence that Parkinson’s Disease Is a Prion Disorder, Which Originates in the Gut?
Authors: Kujawska Małgorzata , Jodynis-Liebert Jadwiga
Published: November 2018

Parkinson’s disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects’ research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.
Novel Findings of Anti-Filarial Drug Target and Structure-Based Virtual Screening for Drug Discovery
Authors: Choi Tae-Woo , Cho Jeong Hoon , Ahnn Joohong , Song Hyun-Ok
Published: November 2018

Lymphatic filariasis and onchocerciasis caused by filarial nematodes are important diseases leading to considerable morbidity throughout tropical countries. Diethylcarbamazine (DEC), albendazole (ALB), and ivermectin (IVM) used in massive drug administration are not highly effective in killing the long-lived adult worms, and there is demand for the development of novel macrofilaricidal drugs affecting new molecular targets. A Ca2+ binding protein, calumenin, was identified as a novel and nematode-specific drug target for filariasis, due to its involvement in fertility and cuticle development in nematodes. As sterilizing and killing effects of the adult worms are considered to be ideal profiles of new drugs, calumenin could be an eligible drug target. Indeed, the Caenorhabditis elegans mutant model of calumenin exhibited enhanced drug acceptability to both microfilaricidal drugs (ALB and IVM) even at the adult stage, proving the roles of the nematode cuticle in efficient drug entry. Molecular modeling revealed that structural features of calumenin were only conserved among nematodes (C. elegans, Brugia malayi, and Onchocerca volvulus). Structural conservation and the specificity of nematode calumenins enabled the development of drugs with good target selectivity between parasites and human hosts. Structure-based virtual screening resulted in the discovery of itraconazole (ITC), an inhibitor of sterol biosynthesis, as a nematode calumenin-targeting ligand. The inhibitory potential of ITC was tested using a nematode mutant model of calumenin.
From Friend to Enemy: Dissecting the Functional Alteration of Immunoregulatory Components during Pancreatic Tumorigenesis
Authors: Wang Hui-Ching , Hung Wen-Chun , Chen Li-Tzong , Pan Mei-Ren
Published: November 2018

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of approximately 8%. More than 80% of patients are diagnosed at an unresectable stage due to metastases or local extension. Immune system reactivation in patients by immunotherapy may eliminate tumor cells and is a new strategy for cancer treatment. The anti-CTLA-4 antibody ipilimumab and anti-PD-1 antibodies pembrolizumab and nivolumab have been approved for cancer therapy in different countries. However, the results of immunotherapy on PDAC are unsatisfactory. The low response rate may be due to poor immunogenicity with low tumor mutational burden in pancreatic cancer cells and desmoplasia that prevents the accumulation of immune cells in tumors. The immunosuppressive tumor microenvironment in PDAC is important in tumor progression and treatment resistance. Switching from an immune tolerance to immune activation status is crucial to overcome the inability of self-defense in cancer. Therefore, thoroughly elucidation of the roles of various immune-related factors, tumor microenvironment, and tumor cells in the development of PDAC may provide appropriate direction to target inflammatory pathway activation as a new therapeutic strategy for preventing and treating this cancer.
Discovery of Heterotopic Bone-Inducing Activity in Hard Tissues and the TGF-β Superfamily
Authors: Katagiri Takenobu , Tsukamoto Sho , Nakachi Yutaka , Kuratani Mai
Published: November 2018

Bone is a unique organ because it can be experimentally induced in soft tissues by implanting a single growth factor, bone morphogenetic protein (BMP). Heterotopic bone-inducing activity was found in demineralized bone matrix in 1965. The characterization of this activity in bone enabled the purification and molecular cloning of BMPs and showed that they are members of the transforming growth factor-β (TGF-β) superfamily. Assay systems developed for this bone-inducing activity revealed the molecular mechanisms of the intracellular signaling of members of the superfamily, including BMPs. Moreover, they are being applied to elucidate molecular mechanisms and to develop novel therapeutics for a disease caused by an abnormality in BMP signaling.
Polygonatum odoratum Polysaccharides Modulate Gut Microbiota and Mitigate Experimentally Induced Obesity in Rats
Authors: Wang Yan , Fei Yanquan , Liu Lirui , Xiao Yunhua , Pang Yilin , Kang Jinhe , Wang Zheng
Published: November 2018

Increasing evidence suggests that the gut microbiota plays vital roles in metabolic diseases. Polygonatum odoratum extract alleviates hyperglycemia and hyperlipidemia, but the underlying mechanism remains unclear. This study investigated the effects of P. odoratum polysaccharides (POPs) on high-fat diet (HFD)-induced obesity in rats and whether these effects were related to modulation of gut microbiota. POP treatment attenuated weight gain, fat accumulation, epididymal adipocyte size, liver triglycerides, and total liver cholesterol content in HFD-fed rats. POP administration also increased short-chain fatty acids (SCFAs), including isobutyric acid, butyric acid, and valeric acid. POP upregulated the expression of genes involved in adipocyte differentiation (Pparg, Cebpa, Cebpb) and lipolysis (Ppara, Atgl), and downregulated those related to lipid synthesis (Srebpf1, Fabp4, Fas), with corresponding changes in PPARγ and FABP4 protein expression. Finally, POP enhanced species richness and improved the gut microbiota community structure, reducing the relative abundances of Clostridium, Enterococcus, Coprobacillus, Lactococcus, and Sutterella. Principal coordinates analysis (PCoA) revealed a clear separation between HFD-fed rats and all other treatment groups. Correlation analysis identified negative and positive associations between obesity phenotypes and 28 POP-influenced operational taxonomic units (OTUs), including putative SCFA-producing bacteria. Our data suggest that POP supplementation may attenuate features of obesity in HFD-fed rats in association with the modulation of gut microbiota.
Metabolomic Signature in Sera of Multiple Sclerosis Patients during Pregnancy
Authors: Rossi Claudia , Cicalini Ilaria , Zucchelli Mirco , Di Ioia Maria , Onofrj Marco , Federici Luca , Del Boccio Piero , Pieragostino Damiana
Published: November 2018

Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures. To gain a deeper inside into the biochemical mechanism of such a multifactorial disease, we adopted targeted metabolomics approaches for the determination of many serum metabolites in 12 pregnant women affected by MuS by mass spectrometry analysis. Our data show a characteristic hormonal fluctuation for estrogens and progesterone, as expected. They also highlight other interesting hormonal alterations for cortisol, corticosterone, 11-deoxycortisol, 4-androstene-3,17-dione, testosterone, and 17α-hydroxyprogesterone. Furthermore, a negative correlation with progesterone levels was observed for amino acids and for acylcarnitines, while an imbalance of different sphingolipids pathways was found during pregnancy. In conclusion, these data are in agreement with the characteristic clinical signs of MuS patients during pregnancy and, if confirmed, they may add an important tessera in the complex mosaic of maternal neuroprotection.
Identification of Heterotrimeric G Protein γ3 Subunit in Rice Plasma Membrane
Authors: Nishiyama Aki , Matsuta Sakura , Chaya Genki , Itoh Takafumi , Miura Kotaro , Iwasaki Yukimoto
Published: November 2018

Heterotrimeric G proteins are important molecules for regulating plant architecture and transmitting external signals to intracellular target proteins in higher plants and mammals. The rice genome contains one canonical α subunit gene (RGA1), four extra-large GTP-binding protein genes (XLGs), one canonical β subunit gene (RGB1), and five γ subunit genes (tentatively named RGG1, RGG2, RGG3/GS3/Mi/OsGGC1, RGG4/DEP1/DN1/OsGGC3, and RGG5/OsGGC2). RGG1 encodes the canonical γ subunit; RGG2 encodes the plant-specific type of γ subunit with additional amino acid residues at the N-terminus; and the remaining three γ subunit genes encode the atypical γ subunits with cysteine abundance at the C-terminus. We aimed to identify the RGG3/GS3/Mi/OsGGC1 gene product, Gγ3, in rice tissues using the anti-Gγ3 domain antibody. We also analyzed the truncated protein, Gγ3∆Cys, in the RGG3/GS3/Mi/OsGGC1 mutant, Mi, using the anti-Gγ3 domain antibody. Based on nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, the immunoprecipitated Gγ3 candidates were confirmed to be Gγ3. Similar to α (Gα) and β subunits (Gβ), Gγ3 was enriched in the plasma membrane fraction, and accumulated in the flower tissues. As RGG3/GS3/Mi/OsGGC1 mutants show the characteristic phenotype in flowers and consequently in seeds, the tissues that accumulated Gγ3 corresponded to the abnormal tissues observed in RGG3/GS3/Mi/OsGGC1 mutants.
Transport of Apolipoprotein B-Containing Lipoproteins through Endothelial Cells Is Associated with Apolipoprotein E-Carrying HDL-Like Particle Formation
Authors: Yang Hong , Zhang Ningya , Okoro Emmanuel U. , Guo Zhongmao
Published: November 2018

Passage of apolipoprotein B-containing lipoproteins (apoB-LPs), i.e., triglyceride-rich lipoproteins (TRLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs), through the endothelial monolayer occurs in normal and atherosclerotic arteries. Among these lipoproteins, TRLs and IDLs are apoE-rich apoB-LPs (E/B-LPs). Recycling of TRL-associated apoE has been shown to form apoE-carrying high-density lipoprotein (HDL)-like (HDLE) particles in many types of cells. The current report studied the formation of HDLE particles by transcytosis of apoB-LPs through mouse aortic endothelial cells (MAECs). Our data indicated that passage of radiolabeled apoB-LPs, rich or poor in apoE, through the MAEC monolayer is inhibited by filipin and unlabeled competitor lipoproteins, suggesting that MAECs transport apoB-LPs via a caveolae-mediated pathway. The cholesterol and apoE in the cell-untreated E/B-LPs, TRLs, IDLs, and LDLs distributed primarily in the low-density (LD) fractions (d ≤ 1.063). A substantial portion of the cholesterol and apoE that passed through the MAEC monolayer was allotted into the high-density (HD) (d > 1.063) fractions. In contrast, apoB was detectable only in the LD fractions before or after apoB-LPs were incubated with the MAEC monolayer, suggesting that apoB-LPs pass through the MAEC monolayer in the forms of apoB-containing LD particles and apoE-containing HD particles.