bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic Emission Characteristics During Rock Fragmentation Processes Induced by Disc Cutter under Different Water Content Conditions
Authors: Lin Qibin , Cao Ping , Cao Rihong , Fan Xiang
Published: January 2019

Based on a properly modified testing platform and Physical Acoustics Corporation (PAC) Micro-II acoustic emission (AE) system, a series of sequential indentation tests on granite samples with five different water contents was conducted to investigate the effect of the water content on the rock fragmentation process induced by a tunnel boring machine (TBM) disc cutter. During these tests, the effects of the water content on the characteristics of the peak penetration force, AE events, consumed energy, rock chip volume, and specific energy were analyzed. The results showed that the AE events were associated with the whole second indentation process of the granite. Under conditions with the same water content, the peak penetration forces and the consumed energy were smaller than those in the first indentation force. Additionally, subsequent chips were formed more frequently than the first indentation chips. The specific energy was lower, which meant that the rock breaking efficiency was higher. With the increase in the water content, the acoustic emission events reduced. The peak penetration force and consumed energy decreased with the increase in the water content. The volume of the chips increased significantly as the water content increased. The specific energy was promoted by the increase of the water content and then by the increase in the rock-breaking efficiency of the TBM disc cutter.
The Effect of Compactness on Laser Cutting of Cathode for Lithium-Ion Batteries Using Continuous Fiber Laser
Authors: Lee Dongkyoung , Oh Byungmoon , Suk Jungdon
Published: January 2019

Lithium-Ion Batteries (LIB) are growing in popularity for many applications. Much research has been focusing on battery performance improvement. However, few studies have overcome the disadvantages of the conventional LIB manufacturing processes. Laser cutting of electrodes has been applied. However, the effect of electrodes’ chemical, physical, and geometrical characteristics on the laser cutting has not been considered. This study proposes the effect of compression of cathode on laser cutting for lithium-ion batteries. The kerf width and top width of the specimens with laser irradiation are measured and the material removal energy is obtained. Observations of SEM photographs and absorptivity measurements are conducted. Increasing volume energies causes logarithmic increases in the kerf and top width. It is observed that the compressed cathode forms a wider kerf width than the uncompressed cathode under the same laser parameters. The top width of the uncompressed cathode is wider than the uncompressed cathode. The compression has a favorable effect on uniform cutting and selective removal of an active electrode.
Whitebark and Foxtail Pine in Yosemite, Sequoia, and Kings Canyon National Parks: Initial Assessment of Stand Structure and Condition
Authors: Nesmith Jonathan C.B. , Wright Micah , Jules Erik S. , McKinney Shawn T.
Published: January 2019

The Inventory & Monitoring Division of the U.S. National Park Service conducts long-term monitoring to provide park managers information on the status and trends in biological and environmental attributes including white pines. White pines are foundational species in many subalpine ecosystems and are currently experiencing population declines. Here we present results on the status of whitebark and foxtail pine in the southern Sierra Nevada of California, an area understudied relative to other parts of their ranges. We selected random plot locations in Yosemite, Sequoia, and Kings Canyon national parks using an equal probability spatially-balanced approach. Tree- and plot-level data were collected on forest structure, composition, demography, cone production, crown mortality, and incidence of white pine blister rust and mountain pine beetle. We measured 7899 whitebark pine, 1112 foxtail pine, and 6085 other trees from 2012–2017. All factors for both species were spatially highly variable. Whitebark pine occurred in nearly-pure krummholz stands at or near treeline and as a minor component of mixed species forests. Ovulate cones were observed on 25% of whitebark pine and 69% of foxtail pine. Whitebark pine seedlings were recorded in 58% of plots, and foxtail pine seedlings in only 21% of plots. Crown mortality (8% in whitebark, 6% in foxtail) was low and significantly higher in 2017 compared to previous years. Less than 1% of whitebark and zero foxtail pine were infected with white pine blister rust and <1% of whitebark and foxtail pine displayed symptoms of mountain pine beetle attack. High elevation white pines in the southern Sierra Nevada are healthy compared to other portions of their range where population declines are significant and well documented. However, increasing white pine blister rust and mountain pine beetle occurrence, coupled with climate change projections, portend future declines for these species, underscoring the need for broad-scale collaborative monitoring.
Unravelling the Effects of Soluble Dietary Fibre Supplementation on Energy Intake and Perceived Satiety in Healthy Adults: Evidence from Systematic Review and Meta-Analysis of Randomised-Controlled Trials
Authors: Salleh Siti Nurshabani , Fairus Ahmad Adli Hamizi , Zahary Mohd Nizam , Bhaskar Raj Naresh , Mhd Jalil Abbe Maleyki
Published: January 2019

Consumption of soluble dietary fibre is recommended as part of a healthy diet. Evidence has shown that soluble dietary fibre slows gastric emptying, increases perceived satiety and plays a significant role in appetite regulation. This systematic review examined the effects of soluble dietary fibre using randomised-controlled trials (RCTs). Three different electronic databases were used, namely PubMed, Scopus® and the Cochrane Central Register of Controlled Trials (CENTRAL). Effect size (Cohen’s d) was calculated based on the intergroup mean difference and standard deviation (SD) followed by Cochran’s Q and I2 determination. The effect size was statistically pooled in the meta-analyses and presented as a forest plot. The risk of bias was high for each study as assessed using the Jadad scale. Meta-analysis of statistically pooled data for guar gum showed a sizeable effect on post-meal energy intake, followed by β-glucan, alginate, polydextrose and pectin, with pooled effect sizes of −0.90, −0.44, −0.42, −0.36 and −0.26, respectively. Guar gum (5 g) effectively reduced energy intake when prepared in milk beverages compared with control milk (p < 0.001). Alginate, when prepared in liquid (5 g) or solid (9 g) meals, effectively reduced energy intake compared with control (p < 0.001). A high dose of polydextrose (25 g) prepared in liquid meal form significantly reduced energy intake (p = 0.01). This study suggests that soluble fibres are not all created equal. Further interventional studies are needed to determine whether combinations of these soluble fibres might have greater effects than individual fibres per se.
Biogenic Amine Production by Lactic Acid Bacteria: A Review
Authors: Barbieri Federica , Montanari Chiara , Gardini Fausto , Tabanelli Giulia
Published: January 2019

Lactic acid bacteria (LAB) are considered as the main biogenic amine (BA) producers in fermented foods. These compounds derive from amino acid decarboxylation through microbial activities and can cause toxic effects on humans, with symptoms (headache, heart palpitations, vomiting, diarrhea) depending also on individual sensitivity. Many studies have focused on the aminobiogenic potential of LAB associated with fermented foods, taking into consideration the conditions affecting BA accumulation and enzymes/genes involved in the biosynthetic mechanisms. This review describes in detail the different LAB (used as starter cultures to improve technological and sensorial properties, as well as those naturally occurring during ripening or in spontaneous fermentations) able to produce BAs in model or in real systems. The groups considered were enterococci, lactobacilli, streptococci, lactococci, pediococci, oenococci and, as minor producers, LAB belonging to Leuconostoc and Weissella genus. A deeper knowledge of this issue is important because decarboxylase activities are often related to strains rather than to species or genera. Moreover, this information can help to improve the selection of strains for further applications as starter or bioprotective cultures, in order to obtain high quality foods with reduced BA content.
A Novel Method for Identifying Essential Genes by Fusing Dynamic Protein–Protein Interactive Networks
Authors: Zhang Fengyu , Peng Wei , Yang Yunfei , Dai Wei , Song Junrong
Published: January 2019

Essential genes play an indispensable role in supporting the life of an organism. Identification of essential genes helps us to understand the underlying mechanism of cell life. The essential genes of bacteria are potential drug targets of some diseases genes. Recently, several computational methods have been proposed to detect essential genes based on the static protein–protein interactive (PPI) networks. However, these methods have ignored the fact that essential genes play essential roles under certain conditions. In this work, a novel method was proposed for the identification of essential proteins by fusing the dynamic PPI networks of different time points (called by FDP). Firstly, the active PPI networks of each time point were constructed and then they were fused into a final network according to the networks’ similarities. Finally, a novel centrality method was designed to assign each gene in the final network a ranking score, whilst considering its orthologous property and its global and local topological properties in the network. This model was applied on two different yeast data sets. The results showed that the FDP achieved a better performance in essential gene prediction as compared to other existing methods that are based on the static PPI network or that are based on dynamic networks.
Neptunium Reactivity During Co-Precipitation and Oxidation of Fe(II)/Fe(III) (Oxyhydr)oxides
Authors: Roberts Hannah E. , Morris Katherine , Mosselmans J. Frederick W. , Law Gareth T. W. , Shaw Samuel
Published: January 2019

Fe(II) bearing iron (oxyhydr)oxides were directly co-precipitated with Np(V)O2+ under anaerobic conditions to form Np doped magnetite and green rust. These environmentally relevant mineral phases were then characterised using geochemical and spectroscopic analyses. The Np doped mineral phases were then oxidised in air over 224 days with solution chemistry and end-point oxidation solid samples collected for further characterisation. Analysis using chemical extractions and X-ray absorption spectroscopy (XAS) techniques confirmed that Np(V) was initially reduced to Np(IV) during co-precipitation of both magnetite and green rust. Extended X-Ray Absorption Fine Structure (EXAFS) modelling suggested the Np(IV) formed a bidentate binuclear sorption complex to both minerals. Furthermore, following oxidation in air over several months, the sorbed Np(IV) was partially oxidised to Np(V), but very little remobilisation to solution occurred during oxidation. Here, linear combination fitting of the X-Ray Absorption Near Edge Structure (XANES) for the end-point oxidation samples for both mineral phases suggested approximately 50% oxidation to Np(V) had occurred over 7 months of oxidation in air. Both the reduction of Np(V) to Np(IV) and inner sphere sorption in association with iron (oxyhydr)oxides, and the strong retention of Np(IV) and Np(V) species with these phases under robust oxidation conditions, have important implications in understanding the mobility of neptunium in a range of engineered and natural environments.
[Mis-]managing Fisheries on the West Coast of Ireland in the Nineteenth Century
Authors: Roney John B.
Published: January 2019

This study focuses on the cultural heritage of artisan coastal fishing in the west of Ireland in the 19th century. The town and port of Dingle, County Kerry, offers an important case study on the progress of local development and changing British policies. While there was clearly an abundance of fish, the poverty and the lack of capital for improvements in ports, vessels, gear, education, and transportation, left the fishing industry underdeveloped until well after the 1890s. In addition, a growing rift developed between the traditional farmer-fishermen and the new middle-class capitalist companies. After several royal commissions examined the fishing industry, the leading ichthyologists of the day concluded that an abundance of fish could be taken without fear of overfishing. The utilitarian economic principle became dominant, changing the previous non-interventionist policies. In the end, there was little concern for sustainability. The mismanagement of commercial fishing in the west of Ireland stemmed from a series of factors, including the increasing need for protein in Britain, technological developments that allowed greater fish catch, and the Conservative government’s political policy of ‘constructive unionism’ that attempted to develop the Irish economy to preserve the kingdom.
Perceptions of Chinese Towards Dementia in Hong Kong—Diagnosis, Symptoms and Impacts
Authors: Lam Tai Pong , Sun Kai Sing , Chan Hoi Yan , Lau Chak Sing , Lam Kwok Fai , Sanson-Fisher Robert
Published: January 2019

The increasing prevalence of dementia has become a public health issue worldwide including China. This study aims to explore the perception of Chinese in Hong Kong towards the diagnosis, symptoms and impacts of dementia. A cross-sectional survey was conducted among outpatients (without diagnosed dementia) attending a regional public hospital using a standard questionnaire. The results from 290 respondents showed that most preferred to be told about the diagnosis of dementia as soon as possible if they got it, in order to deal with the news and to access treatment and support early. Nearly two thirds of the respondents perceived practical issues (61.3%), physical health (61.0%), and emotional distress (58.4%) as their most fearful impacts, while legal issues (7.4%) were their least concerns. Family history/genes (79.1%) and brain injury (75.9%) were the most commonly perceived causes of dementia. For symptoms, respondents were more likely to identify cognitive impairments than undesirable behaviours. The accepting and proactive attitudes of the public indicate that there is a timely need of more public education about the disease, early screening and better continuity of care to fulfil the anticipated increase of the dementia patient population.
Effect of Benzene Exposure on the Urinary Biomarkers of Nucleic Acid Oxidation in Two Cohorts of Gasoline Pump Attendants
Authors: Carrieri Mariella , Pigini Daniela , Martinelli Andrea , Paci Enrico , Maratini Federica , Salamon Fabiola , Tranfo Giovanna
Published: January 2019

(1) Background: The oxidized guanine derivatives excreted into urine, products of DNA and RNA oxidation and repair, are used as biomarkers of oxidative damage in humans. This study aims to evaluate oxidative damage in gasoline pump attendants occupationally exposed to benzene. Benzene is contained in the gasoline but it is also produced from traffic and from smoking. (2) Methods: Twenty-nine gasoline pump attendants from two major cities of Saudi Arabia and 102 from Italy were studied for urinary 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and S-phenyl-mercapturic acid (SPMA) for benzene exposure and urinary cotinine for smoking status assessment by liquid chromatography-tandem mass spectrometry. Airborne benzene was also assessed in the Italian group by gas-chromatography with flame ionization detector (GC-FID). (3) Results: The results suggest that high levels of benzene exposure can cause an accumulation of SPMA and bring about the formation of the oxidation biomarkers studied to saturation. At low exposure levels, SPMA and oxidation biomarker levels were correlated among them and were associated with the smoking habit. (4) Conclusions: The study confirms the association between benzene exposure and the excretion of nucleic acid oxidation biomarkers and enhances the importance of measuring the smoking habit, as it can significantly influence oxidative damage, especially when the exposure levels are low.
Mortality from Homicides in Slums in the City of Belo Horizonte, Brazil: An Evaluation of the Impact of a Re-Urbanization Project
Authors: De Salles Dias Maria , De Lima Friche Amélia , Mingoti Sueli , Da Silva Costa Dário , De Souza Andrade Amanda , Freire Fernando , De Oliveira Veneza , Teixeira Caiaffa Waleska
Published: January 2019

Background: Homicide rates in Brazil are among the highest worldwide. Although not exclusive to large Brazilian cities, homicides find their most important determinants in cities’ slums. In the last decade, an urban renewal process has been initiated in the city of Belo Horizonte, in Brazil. Named Vila Viva project, it includes structuring urban interventions such as urban renewal, social development actions and land regularization in the slums of the city. This study evaluates the project’s effect on homicide rates according to time and interventions. Methods: Homicide rates were analyzed comparing five slums with interventions (S1–S5) to five grouped non-intervened slums (S0), with similar socioeconomic characteristics from 2002 to 2012. Poisson regression model estimates the effect of time of observation and the effect of time of exposure (in years) to a completed intervention, besides the overall risk ratio (RR). Results: Using the time of observation in years, homicide rates decreased in the studied period and even more if considered cumulative time of exposure to a completed intervention for S1, S2, S3 and S4, but not for S5. Conclusions: Although the results of the effect of the interventions are not repeated in all slums, a downward trend in homicide rates has been found, which is connected to the interventions. New approaches could be necessary in order to verify the nexus between slum renewal projects and the reduction of homicide rates.
A GIS-Based Artificial Neural Network Model for Spatial Distribution of Tuberculosis across the Continental United States
Authors: Mollalo Abolfazl , Mao Liang , Rashidi Parisa , Glass Gregory E.
Published: January 2019

Despite the usefulness of artificial neural networks (ANNs) in the study of various complex problems, ANNs have not been applied for modeling the geographic distribution of tuberculosis (TB) in the US. Likewise, ecological level researches on TB incidence rate at the national level are inadequate for epidemiologic inferences. We collected 278 exploratory variables including environmental and a broad range of socio-economic features for modeling the disease across the continental US. The spatial pattern of the disease distribution was statistically evaluated using the global Moran’s I, Getis–Ord General G, and local Gi* statistics. Next, we investigated the applicability of multilayer perceptron (MLP) ANN for predicting the disease incidence. To avoid overfitting, L1 regularization was used before developing the models. Predictive performance of the MLP was compared with linear regression for test dataset using root mean square error, mean absolute error, and correlations between model output and ground truth. Results of clustering analysis showed that there is a significant spatial clustering of smoothed TB incidence rate (p < 0.05) and the hotspots were mainly located in the southern and southeastern parts of the country. Among the developed models, single hidden layer MLP had the best test accuracy. Sensitivity analysis of the MLP model showed that immigrant population (proportion), underserved segments of the population, and minimum temperature were among the factors with the strongest contributions. The findings of this study can provide useful insight to health authorities on prioritizing resource allocation to risk-prone areas.
Evidence-Based Phytoiatry, a New Approach in Crop Protection
Authors: Iriti Marcello , Varoni Elena Maria
Published: January 2019

In the past decades, the scientific quality of biomedical studies has been hierarchically depicted in the well-known pyramid of evidence-based medicine (EBM), with higher and higher levels of evidence moving from the base to the top. Such an approach is missing in the modern crop protection and, therefore, we introduce, for the first time, this novel concept of evidence-based phytoiatry in this field. This editorial is not a guideline on plant protection products (PPP) registration, but rather a scientific and technical support for researchers involved in the general area of plant pathology, providing them with evidence-based information useful to design critically new studies.
Anti-Colitic Effects of Ethanol Extract of Persea americana Mill. through Suppression of Pro-Inflammatory Mediators via NF-κB/STAT3 Inactivation in Dextran Sulfate Sodium-Induced Colitis Mice
Authors: Hong Joo Young , Chung Kyung-Sook , Shin Ji-Sun , Park Geonha , Jang Young Pyo , Lee Kyung-Tae
Published: January 2019

Persea americana Mill, cv. Hass, also known as avocado, has been reported to possess hypolipidemic, anti-diabetic, anti-oxidant, cardioprotective, and photoprotective potencies. However, few studies have reported its anti-colitic effects. In this study, we investigated anti-colitic effects of ethanol extract of P. americana (EEP) in dextran sulfate sodium (DSS)-induced colitic mice and the involved molecular mechanisms. EEP effectively improved clinical signs and histological characteristics of DSS-induced colitis mice. In DSS-exposed colonic tissues, EEP reduced expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. Moreover, EEP suppressed DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Consistent with in vivo results, EEP also suppressed protein and mRNA expression levels of iNOS, COX-2, and pro-inflammatory cytokines via NF-κB and STAT3 inactivation in LPS-induced RAW 264.7 macrophages. Taken together, our data indicate that ethanol extract of avocado may be used as a promising therapeutic against inflammatory bowel diseases by suppressing the NF-κB and STAT3 signaling pathway.
Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells
Authors: Chen Ta-Ching , She Pin-Yi , Chen Dong Feng , Lu Jui-Hsien , Yang Chang-Hao , Huang Ding-Siang , Chen Pao-Yang , Lu Chen-Yu , Cho Kin-Sang , Chen Hsin-Fu , Su Wei-Fang
Published: January 2019

Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.
Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases
Authors: Huang Qi-Yuan , Lai Xing-Ning , Qian Xian-Ling , Lv Lin-Chen , Li Jun , Duan Jing , Xiao Xing-Hua , Xiong Li-Xia
Published: January 2019

Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.
Ontogenetic Changes in Auxin Biosynthesis and Distribution Determine the Organogenic Activity of the Shoot Apical Meristem in pin1 Mutants
Authors: Banasiak Alicja , Biedroń Magdalena , Dolzblasz Alicja , Berezowski Mateusz Adam
Published: January 2019

In the shoot apical meristem (SAM) of Arabidopsis, PIN1-dependent polar auxin transport (PAT) regulates two crucial developmental processes: organogenesis and vascular system formation. However, the knockout mutation in the PIN1 gene does not fully inhibit these two processes. Therefore, we investigated a potential source of auxin for organogenesis and vascularization during inflorescence stem development. We analyzed auxin distribution in wild-type (WT) and pin1 mutant plants using a refined protocol of auxin immunolocalization; auxin activity, with the response reporter pDR5:GFP; and expression of auxin biosynthesis genes YUC1 and YUC4. Our results revealed that regardless of the functionality of PIN1-mediated PAT, auxin is present in the SAM and vascular strands. In WT plants, auxin always accumulates in all cells of the SAM, whereas in pin1 mutants, its localization within the SAM changes ontogenetically and is related to changes in the structure of the vascular system, organogenic activity of SAM, and expression levels of YUC1 and YUC4 genes. Our findings indicate that the presence of auxin in the meristem of pin1 mutants is an outcome of at least two PIN1-independent mechanisms: acropetal auxin transport from differentiated tissues with the use of vascular strands and auxin biosynthesis within the SAM.
Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity
Authors: Scheu Stefanie , Ali Shafaqat , Mann-Nüttel Ritu , Richter Lisa , Arolt Volker , Dannlowski Udo , Kuhlmann Tanja , Klotz Luisa , Alferink Judith
Published: January 2019

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and axonal damage. It often affects young adults and can lead to neurological disability. Interferon β (IFNβ) preparations represent widely used treatment regimens for patients with relapsing-remitting MS (RRMS) with therapeutic efficacy in reducing disease progression and frequency of acute exacerbations. In mice, IFNβ therapy has been shown to ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of MS while genetic deletion of IFNβ or its receptor augments clinical severity of disease. However, the complex mechanism of action of IFNβ in CNS autoimmunity has not been fully elucidated. Here, we review our current understanding of the origin, phenotype, and function of microglia and CNS immigrating macrophages in the pathogenesis of MS and EAE. In addition, we highlight the emerging roles of microglia as IFNβ-producing cells and vice versa the impact of IFNβ on microglia in CNS autoimmunity. We finally discuss recent progress in unraveling the underlying molecular mechanisms of IFNβ-mediated effects in EAE.
Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells
Authors: Nie Jun-Hua , Li Hong , Wu Mo-Li , Lin Xiao-Min , Xiong Le , Liu Jia
Published: January 2019

Glioblastoma multiforme (GBM) is the commonest primary brain malignancy with extremely poor prognosis. Resveratrol posseses anti-cancer effects, while GBM cells respond differently to it due to certain unknown reason(s). Because the tumor-derived exosomes are supposed to influence chemosensitivity, the exosomic proteins released from resveratrol-sensitive U251 and resveratrol-resistant glioblastoma LN428 cells are profiled before (N/Exo) and after drug treatment (Res/Exo) by label-free liquid chromatography-mass spectrometry (LC-MS). The therapeutic implications of the proteomic findings are estimated by gene ontology enrichment analysis (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based bioinformatic analyses and further elucidated by exosome co-incubating. The results reveal that U251/N/Exo but not U251/Res/Exo enhances resveratrol sensitivity of resveratrol-resistant LN428 cells. The resveratrol sensitive properties of U251 cells are not altered by either LN428/N/Exo or LN428/Res/Exo. U251/N/Exo contains higher levels of chromatin silencing and epidermis development proteins, while U251/Res/Exo has more oxygen transport and G protein-coupled receptor. Both of LN428/N/Exo and LN428/Res/Exo are rich in the proteins related with nucleosome assembly, microtubule-based process and chromatin silencing. In conclusion, U251/N/Exo sensitizes LN428 cells to resveratrol via delivering drug sensitizing signals, suggesting the presence of additional factor(s) that may determine the resveratrol sensitivities of glioblastoma cells.
The Fate of Transplanted Periodontal Ligament Stem Cells in Surgically Created Periodontal Defects in Rats
Authors: Iwasaki Kengo , Akazawa Keiko , Nagata Mizuki , Komaki Motohiro , Honda Izumi , Morioka Chikako , Yokoyama Naoki , Ayame Hirohito , Yamaki Kazumasa , Tanaka Yuichi , Kimura Tsuyoshi , Kishida Akio , Watabe Tetsuro , Morita Ikuo
Published: January 2019

Periodontal disease is chronic inflammation that leads to the destruction of tooth-supporting periodontal tissues. We devised a novel method (“cell transfer technology”) to transfer cells onto a scaffold surface and reported the potential of the technique for regenerative medicine. The aim of this study is to examine the efficacy of this technique in periodontal regeneration and the fate of transplanted cells. Human periodontal ligament stem cells (PDLSCs) were transferred to decellularized amniotic membrane and transplanted into periodontal defects in rats. Regeneration of tissues was examined by microcomputed tomography and histological observation. The fate of transplanted PDLSCs was traced using PKH26 and human Alu sequence detection by PCR. Imaging showed more bone in PDLSC-transplanted defects than those in control (amnion only). Histological examination confirmed the enhanced periodontal tissue formation in PDLSC defects. New formation of cementum, periodontal ligament, and bone were prominently observed in PDLSC defects. PKH26-labeled PDLSCs were found at limited areas in regenerated periodontal tissues. Human Alu sequence detection revealed that the level of Alu sequence was not increased, but rather decreased. This study describes a novel stem cell transplantation strategy for periodontal disease using the cell transfer technology and offers new insight for cell-based periodontal regeneration.
Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma
Authors: Kuo Selena Z. , Honda Christine O. , Li Wei Tse , Honda Thomas K. , Kim Elizabeth , Altuna Xabier , Abhold Eric , Wang-Rodriguez Jessica , Ongkeko Weg M.
Published: January 2019

Cancer stem cells (CSCs) have been shown as a distinct population of cancer cells strongly implicated with resistance to conventional chemotherapy. Metformin, the most widely prescribed drug for diabetes, was reported to target cancer stem cells in various cancers. In this study, we sought to determine the effects of metformin on head and neck squamous cell carcinoma (HNSCC). CSCs and non-stem HNSCC cells were treated with metformin and cisplatin alone, and in combination, and cell proliferation levels were measured through MTS assays. Next, potential targets of metformin were explored through computational small molecule binding analysis. In contrast to the reported effects of metformin on CSCs in other cancers, our data suggests that metformin protects HNSCC CSCs against cisplatin in vitro. Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG. On the other hand, we observed that metformin successfully decreased the proliferation of non-stem HNSCC cells. Computational drug–protein interaction analysis revealed mitochondrial complex III to be a likely target of metformin. Based on our results, we present the novel hypothesis that metformin targets complex III to reduce reactive oxygen species (ROS) levels, leading to the differential effects observed on non-stem cancer cells and CSCs.
In Vitro Cytotoxicity Evaluation of the Magnéli Phase Titanium Suboxides (TixO2x−1) on A549 Human Lung Cells
Authors: Kononenko Veno , Drobne Damjana
Published: January 2019

The use of titanium suboxides, known as Magnéli phase TiOx, is expected to increase in the near future due to their desirable properties. In order to use Magnéli phase TiOx nanoparticles safely, it is necessary to know how nanoparticles interact with biological systems. In this study, the cytotoxicity of three different Magnéli TiOx nanoparticles was evaluated using human lung A549 cells and the results were compared with hazard data on two different TiO2 nanoparticles whose biological interactions have already been extensively studied. After A549 cells were exposed to nanoparticles, the metabolic activity was measured by the Resazurin assay, the amount of cellular proteins was measured by the Coomassie Blue assay, and lysosomal integrity was measured by the Neutral Red Uptake assay. In order to investigate possible modes of particle actions, intracellular Ca2+ level, reactive oxygen species (ROS) production, and photo-oxidative disruptions of lysosomal membranes were assessed. All experiments were performed in serum-containing and in serum-deprived cell culture mediums. In addition, the photocatalytic activity of Magnéli TiOx and TiO2 nanoparticles was measured. The results show that Magnéli TiOx nanoparticles increase intracellular Ca2+ but not ROS levels. In contrast, TiO2 nanoparticles increase ROS levels, resulting in a higher cytotoxicity. Although Magnéli TiOx nanoparticles showed a lower UV-A photocatalytic activity, the photo-stability of the lysosomal membranes was decreased by a greater extent, possibly due to particle accumulation inside lysosomes. We provide evidence that Magnéli TiOx nanoparticles have lower overall biological activity when compared with the two TiO2 formulations. However, some unique cellular interactions were detected and should be further studied in line with possible Magnéli TiOx application. We conclude that Magnéli phase nanoparticles could be considered as low toxic material same as other forms of titanium oxide particles.
Detection of Low-Frequency Mutations and Identification of Heat-Induced Artifactual Mutations Using Duplex Sequencing
Authors: Ahn Eun Hyun , Lee Seung Hyuk
Published: January 2019

We present a genome-wide comparative and comprehensive analysis of three different sequencing methods (conventional next generation sequencing (NGS), tag-based single strand sequencing (e.g., SSCS), and Duplex Sequencing for investigating mitochondrial mutations in human breast epithelial cells. Duplex Sequencing produces a single strand consensus sequence (SSCS) and a duplex consensus sequence (DCS) analysis, respectively. Our study validates that although high-frequency mutations are detectable by all the three sequencing methods with the similar accuracy and reproducibility, rare (low-frequency) mutations are not accurately detectable by NGS and SSCS. Even with conservative bioinformatical modification to overcome the high error rate of NGS, the NGS frequency of rare mutations is 7.0 × 10−4. The frequency is reduced to 1.3 × 10−4 with SSCS and is further reduced to 1.0 × 10−5 using DCS. Rare mutation context spectra obtained from NGS significantly vary across independent experiments, and it is not possible to identify a dominant mutation context. In contrast, rare mutation context spectra are consistently similar in all independent DCS experiments. We have systematically identified heat-induced artifactual variants and corrected the artifacts using Duplex Sequencing. Specific sequence contexts were analyzed to examine the effects of neighboring bases on the accumulation of heat-induced artifactual variants. All of these artifacts are stochastically occurring rare mutations. C > A/G > T, a signature of oxidative damage, is the most increased (170-fold) heat-induced artifactual mutation type. Our results strongly support the claim that Duplex Sequencing accurately detects low-frequency mutations and identifies and corrects artifactual mutations introduced by heating during DNA preparation.
Population Genetics Revealed a New Locus That Underwent Positive Selection in Barley
Authors: Reinert Stephan , Osthoff Alina , Léon Jens , Naz Ali Ahmad
Published: January 2019

Trait variation among natural populations and their cultivated relatives occurs due to evolutionary forces, including selection and drift. In the present study, we analyzed these forces at the locus level in a global barley diversity set using population genetics analysis. Genome-wide outlier loci detection found a locus on chromosome 2H at which a common single nucleotide polymorphism (SNP) marker SCRI_RS_170235 accounted for the highest diversity index (Fst) values between cultivars and landraces and between cultivars and wild accessions. For a population wide genetic analysis, we developed a Polymerase Chain Reaction (PCR)-based cleaved amplified polymorphic marker at the identified locus. Marker genotyping of 115 genotypes identified a characteristic distribution of polymorphisms among the cultivated, landraces, and wild barley accessions. Using this marker, we screened a library of wild barley introgression lines (IL) and selected IL S42IL-109 that carried the wild introgression of the outlier locus in cultivar ‘Scarlett’ background. A plethora of phenotypic evaluation was performed between the S42IL109 and ‘Scarlett’ to dissect the putative effect of the identified outlier locus. Comparison of S42IL109 and ‘Scarlett’ revealed significant difference in the development of phyllochron two (Phyl-2), phyllochron three (Phyl-3), and phyllochron four (Phyl-4). Across the three phyllochrons, it was consistently observed that S42IL109 developed successive leaves in a shorter time span, by one to two days, compared to ‘Scarlett’. These data suggest that outlier locus may influence phyllochron variation which underwent positive selection in barley.
OsMGT1 Confers Resistance to Magnesium Deficiency By Enhancing the Import of Mg in Rice
Authors: Zhang Ludan , Peng Yuyang , Li Jian , Tian Xinyue , Chen Zhichang
Published: January 2019

Magnesium (Mg) is an essential nutrient element for plant growth and plays an important role in numerous physiological and biochemical processes. Mg deficiency inhibits plant growth and has become a growing problem for crop productions in agriculture. However, the molecular mechanisms for the resistance to Mg deficiency in plants were not well understood. In this study, we identified a Mg transporter gene OsMGT1 that confers resistance to Mg deficiency in rice (Oryza sativa). The expression of OsMGT1 was highly induced by Mg deficiency in shoots. Investigation of tissue expression patterns revealed that OsMGT1 was mainly expressed in the phloem region; however, Mg deficiency remarkably enhanced its expression in xylem parenchyma and mesophyll cells in shoots. Knockout of OsMGT1 resulted in a significant reduction in Mg content and biomass when grown at Mg-limited conditions. Furthermore, the sensitivity to low-Mg in mutants was intensified by excessive calcium supply. In addition, overexpression of OsMGT1 increased Mg content and biomass under low-Mg supply. In conclusion, our results indicate that OsMGT1 plays an important role in rice Mg import and is required for the resistance to Mg deficiency, which can be utilized for molecular breeding of low-Mg tolerant plants.
Global Phosphoproteomic Analysis Reveals the Defense and Response Mechanisms of Jatropha Curcas Seedling under Chilling Stress
Authors: Liu Hui , Wang Fen-Fen , Peng Xian-Jun , Huang Jian-Hui , Shen Shi-Hua
Published: January 2019

As a promising energy plant for biodiesel, Jatropha curcas is a tropical and subtropical shrub and its growth is affected by one of major abiotic stress, chilling. Therefore, we adopt the phosphoproteomic analysis, physiological measurement and ultrastructure observation to illustrate the responsive mechanism of J. curcas seedling under chilling (4 °C) stress. After chilling for 6 h, 308 significantly changed phosphoproteins were detected. Prolonged the chilling treatment for 24 h, obvious physiological injury can be observed and a total of 332 phosphoproteins were examined to be significantly changed. After recovery (28 °C) for 24 h, 291 phosphoproteins were varied at the phosphorylation level. GO analysis showed that significantly changed phosphoproteins were mainly responsible for cellular protein modification process, transport, cellular component organization and signal transduction at the chilling and recovery periods. On the basis of protein-protein interaction network analysis, phosphorylation of several protein kinases, such as SnRK2, MEKK1, EDR1, CDPK, EIN2, EIN4, PI4K and 14-3-3 were possibly responsible for cross-talk between ABA, Ca2+, ethylene and phosphoinositide mediated signaling pathways. We also highlighted the phosphorylation of HOS1, APX and PIP2 might be associated with response to chilling stress in J. curcas seedling. These results will be valuable for further study from the molecular breeding perspective.
Cytoskeleton, Transglutaminase and Gametophytic Self-Incompatibility in the Malinae (Rosaceae)
Authors: Del Duca Stefano , Aloisi Iris , Parrotta Luigi , Cai Giampiero
Published: January 2019

Self-incompatibility (SI) is a complex process, one out of several mechanisms that prevent plants from self-fertilizing to maintain and increase the genetic variability. This process leads to the rejection of the male gametophyte and requires the co-participation of numerous molecules. Plants have evolved two distinct SI systems, the sporophytic (SSI) and the gametophytic (GSI) systems. The two SI systems are markedly characterized by different genes and proteins and each single system can also be divided into distinct subgroups; whatever the mechanism, the purpose is the same, i.e., to prevent self-fertilization. In Malinae, a subtribe in the Rosaceae family, i.e., Pyrus communis and Malus domestica, the GSI requires the production of female determinants, known as S-RNases, which penetrate the pollen tube to interact with the male determinants. Beyond this, the penetration of S-RNase into the pollen tube triggers a series of responses involving membrane proteins, such as phospholipases, intracellular variations of cytoplasmic Ca2+, production of reactive oxygen species (ROS) and altered enzymatic activities, such as that of transglutaminase (TGase). TGases are widespread enzymes that catalyze the post-translational conjugation of polyamines (PAs) to different protein targets and/or the cross-linking of substrate proteins leading to the formation of cross-linked products with high molecular mass. When actin and tubulin are the substrates, this destabilizes the cytoskeleton and inhibits the pollen-tube’s growth process. In this review, we will summarize the current knowledge of the relationship between S-RNase penetration, TGase activity and cytoskeleton function during GSI in the Malinae.
Molecular Dynamics Simulations of Wild Type and Mutants of SAPAP in Complexed with Shank3
Authors: Piao Lianhua , Chen Zhou , Li Qiuye , Liu Ranran , Song Wei , Kong Ren , Chang Shan
Published: January 2019

Specific interactions between scaffold protein SH3 and multiple ankyrin repeat domains protein 3 (Shank3) and synapse-associated protein 90/postsynaptic density-95–associated protein (SAPAP) are essential for excitatory synapse development and plasticity. In a bunch of human neurological diseases, mutations on Shank3 or SAPAP are detected. To investigate the dynamical and thermodynamic properties of the specific binding between the N-terminal extended PDZ (Post-synaptic density-95/Discs large/Zonaoccludens-1) domain (N-PDZ) of Shank3 and the extended PDZ binding motif (E-PBM) of SAPAP, molecular dynamics simulation approaches were used to study the complex of N-PDZ with wild type and mutated E-PBM peptides. To compare with the experimental data, 974QTRL977 and 966IEIYI970 of E-PBM peptide were mutated to prolines to obtain the M4P and M5P system, respectively. Conformational analysis shows that the canonical PDZ domain is stable while the βN extension presents high flexibility in all systems, especially for M5P. The high flexibility of βN extension seems to set up a barrier for the non-specific binding in this area and provide the basis for specific molecular recognition between Shank3 and SAPAP. The wild type E-PBM tightly binds to N-PDZ during the simulation while loss of binding is observed in different segments of the mutated E-PBM peptides. Energy decomposition and hydrogen bonds analysis show that M4P mutations only disrupt the interactions with canonical PDZ domain, but the interactions with βN1′ remain. In M5P system, although the interactions with βN1′ are abolished, the binding between peptide and the canonical PDZ domain is not affected. The results indicate that the interactions in the two-binding site, the canonical PDZ domain and the βN1′ extension, contribute to the binding between E-PBM and N-PDZ independently. The binding free energies calculated by MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) are in agreement with the experimental binding affinities. Most of the residues on E-PBM contribute considerably favorable energies to the binding except A963 and D964 in the N-terminal. The study provides information to understand the molecular basis of specific binding between Shank3 and SAPAP, as well as clues for design of peptide inhibitors.