bluuebunny/crossref_metadata_2025 huggingface dataset:
The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome
Authors: Gujar Hemant , Weisenberger Daniel J. , Liang Gangning
Published: February 2019

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.
On the Close Relatedness of Two Rice-Parasitic Root-Knot Nematode Species and the Recent Expansion of Meloidogyne graminicola in Southeast Asia
Authors: Besnard Guillaume , Thi-Phan Ngan , Ho-Bich Hai , Dereeper Alexis , Trang Nguyen Hieu , Quénéhervé Patrick , Aribi Jamel , Bellafiore Stéphane
Published: February 2019

Meloidogyne graminicola is a facultative meiotic parthenogenetic root-knot nematode (RKN) that seriously threatens agriculture worldwide. We have little understanding of its origin, genomic structure, and intraspecific diversity. Such information would offer better knowledge of how this nematode successfully damages rice in many different environments. Previous studies on nuclear ribosomal DNA (nrDNA) suggested a close phylogenetic relationship between M. graminicola and Meloidogyne oryzae, despite their different modes of reproduction and geographical distribution. In order to clarify the evolutionary history of these two species and explore their molecular intraspecific diversity, we sequenced the genome of 12 M. graminicola isolates, representing populations of worldwide origins, and two South American isolates of M. oryzae. k-mer analysis of their nuclear genome and the detection of divergent homologous genomic sequences indicate that both species show a high proportion of heterozygous sites (ca. 1–2%), which had never been previously reported in facultative meiotic parthenogenetic RKNs. These analyses also point to a distinct ploidy level in each species, compatible with a diploid M. graminicola and a triploid M. oryzae. Phylogenetic analyses of mitochondrial genomes and three nuclear genomic sequences confirm close relationships between these two species, with M. graminicola being a putative parent of M. oryzae. In addition, comparative mitogenomics of those 12 M. graminicola isolates with a Chinese published isolate reveal only 15 polymorphisms that are phylogenetically non-informative. Eight mitotypes are distinguished, the most common one being shared by distant populations from Asia and America. This low intraspecific diversity, coupled with a lack of phylogeographic signal, suggests a recent worldwide expansion of M. graminicola.
Kinetics of White Soft Minerals (WSMs) Decomposition under Conditions of Interest for Astrobiology: A Theoretical and Experimental Study
Authors: Micca Longo Gaia , D’Elia Marcella , Fonti Sergio , Longo Savino , Mancarella Francesca , Orofino Vincenzo
Published: February 2019

In this paper, the thermal decomposition kinetics of a class of minerals that we call White Soft Minerals (WSMs) is studied by means of theoretical and experimental methods, in connection to the transport of extraterrestrial organic matter to Earth and the possible use of the decomposition reaction in the characterization of these minerals in space. WSMs include, under a single denomination, carbonates and sulphates of Mg, Fe, and Ca. To improve the present knowledge of the properties of such materials, we use the following techniques: kinetic models for chemical decomposition, atmospheric entry models, spectroscopy, and gravimetric analyses. Model results show that the atmospheric entry of WSM grains is strongly affected by their thermal decomposition. The decomposition reaction, being strongly endothermic, tends to significantly lower the grain temperature during the atmospheric entry, especially at high altitudes and for grazing entries. A previously proposed infrared spectroscopic technique to evaluate the degree of advancement of the reaction is found to be in good agreement with gravimetric measurements for calcium carbonate. The numerical model developed for the atmospheric entry scenarios is used to interpret experimental results. These main findings show that an additional contribution to the reaction enthalpy is needed to reproduce the experimental results, suggesting that the present theoretical model needs improvements such as the account of gas diffusion in the materials.
Sulforaphane Cannot Protect Human Fibroblasts From Repeated, Short and Sublethal Treatments with Hydrogen Peroxide
Authors: Lionetti Maria Chiara , Mutti Federico , Soldati Erica , Fumagalli Maria Rita , Coccé Valentina , Colombo Graziano , Astori Emanuela , Miani Alessandro , Milzani Aldo , Dalle-Donne Isabella , Ciusani Emilio , Costantini Giulio , La Porta Caterina A. M.
Published: February 2019

A delicate balance of reactive oxygen species (ROS) exists inside the cell: when the mechanisms that control the level of ROS fail, the cell is in an oxidative stress state, a condition that can accelerate aging processes. To contrast the pro-aging effect of ROS, the supplementation of antioxidants has been recently proposed. Sulforaphane (SFN) is an isothiocyanate isolated from Brassica plants that has been shown to modulate many critical factors inside the cells helping to counteract aging processes. In the present work, we exposed human dermal fibroblast to short, sublethal and repeated treatments with hydrogen peroxide for eight days, without or in combination with low concentration of SFN. Hydrogen peroxide treatments did not affect the oxidative status of the cells, without any significant change of the intracellular ROS levels or the number of mitochondria or thiols in total proteins. However, our regime promoted cell cycle progression and cell viability, increased the anti-apoptotic factor survivin and increased DNA damage, measured as number of foci positive for γ -H2AX. On the other hand, the treatment with SFN alone seemed to exert a protective effect, increasing the level of p53, which can block the expansion of possible DNA damaged cells. However, continued exposure to SFN at this concentration could not protect the cells from stress induced by hydrogen peroxide.
Impacts of Anthropogenic Changes on the Mun River Water: Insight from Spatio-Distributions and Relationship of C and N Species in Northeast Thailand
Authors: Liu Jinke , Han Guilin , Liu Xiaolong , Liu Man , Song Chao , Zhang Qian , Yang Kunhua , Li Xiaoqiang
Published: February 2019

C and N species, including dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), dissolved organic nitrogen (DON), NO3− and NH4+ contents in 57 river water samples collected from the Mun River of Thailand were measured to determine the relationships between these dissolved load species and their impacts on the environment. DOC values varied between 1.71 and 40.08 mg/L, averaging 11.14 mg/L; DON values ranged from 0.20 to 1.37 mg/L, with an average value of 0.48 mg/L; NO3−-N values averaged 0.18 mg/L; and NH4+-N values averaged 0.15 mg/L. DOC contents increased while DON and NO3− values decreased along the flow direction. The concentrations of NH4+ maintained the same level in the whole watershed. DOC and DON values exhibited clearly higher concentrations in comparison with other rivers worldwide and were inextricably linked with anthropogenic inputs. The relationships of DOC, DON, and anthropogenic ions imply that there are two different anthropogenic sources (industrial activities and agricultural activities) of the dissolved load in the Mun River watershed. The limited correlations between the DON, NO3−, and NH4+ indicate that the N species are not dominated by a single factor, and reciprocal transformations of riverine N pool are complex. Based on the environmental water quality standard reported by the EC (European Communities) and the World Health Organization, assessments of the water quality using the parameters of pH, dissolved oxygen (DO), NO3−, NH4+, and TN (total nitrogen) in the Mun River were conducted. The results demonstrate that the river water faces potential environmental pollution, and anthropogenic inputs endanger local water quality and the aquatic community. Therefore, the local government should restrict and reduce the anthropogenic inputs discharged in to rivers, and launch long-term monitoring of water quality.
Association of Circulating Irisin Concentrations with Weight Loss after Roux-en-Y Gastric Bypass Surgery
Authors: Lee Yeon Ji , Heo Yoonseok , Choi Ji-Ho , Park Sunghyouk , Kim Kyoung Kon , Shin Dong Wun , Kang Ju-Hee
Published: February 2019

Irisin is a myokine with potential anti-obesity properties that has been suggested to increase energy expenditure in obese patients. However, there is limited clinical information on the biology of irisin in humans, especially in morbidly obese patients undergoing bariatric surgery. We aimed to assess the association of circulating irisin concentrations with weight loss in obese patients undergoing bariatric surgery. This was a pilot, single-centre, longitudinal observational study. We recruited 25 morbidly obese subjects who underwent Roux-en-Y gastric bypass surgery (RYGBP), and blood samples from 12 patients were taken to measure serum irisin concentrations before, and one and nine months after surgery. Their clinical characteristics were measured for one year. The preoperative serum irisin concentration (mean 1.01 ± 0.23 μg/mL, range 0.73–1.49) changed bidirectionally one month after RYGBP. The mean concentration at nine months was 1.11 ± 0.15 μg/mL (range 0.92–1.35). Eight patients had elevated irisin levels compared with their preoperative values, but four did not. Elevations of irisin levels nine months, but not one month, after surgery, were associated with lower preoperative levels (p = 0.016) and worse weight reduction rates (p = 0.006 for the percentage excess weight loss and p = 0.032 for changes in body mass index). The preoperative serum irisin concentrations were significantly correlated with the percentage of excess weight loss for one year (R2 = 0.612; p = 0.04) in our study. Our results suggest that preoperative circulating irisin concentrations may be at least in part associated with a weight loss effect of bariatric surgery in morbidly obese patients. Further large-scale clinical studies are needed to ratify these findings.
Area-Level Walkability and the Geographic Distribution of High Body Mass in Sydney, Australia: A Spatial Analysis Using the 45 and Up Study
Authors: Mayne Darren J. , Morgan Geoffrey G. , Jalaludin Bin B. , Bauman Adrian E.
Published: February 2019

Improving the walkability of built environments to promote healthy lifestyles and reduce high body mass is increasingly considered in regional development plans. Walkability indexes have the potential to inform, benchmark and monitor these plans if they are associated with variation in body mass outcomes at spatial scales used for health and urban planning. We assessed relationships between area-level walkability and prevalence and geographic variation in overweight and obesity using an Australian population-based cohort comprising 92,157 Sydney respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. Individual-level data on overweight and obesity were aggregated to 2006 Australian postal areas and analysed as a function of area-level Sydney Walkability Index quartiles using conditional auto regression spatial models adjusted for demographic, social, economic, health and socioeconomic factors. Both overweight and obesity were highly clustered with higher-than-expected prevalence concentrated in the urban sprawl region of western Sydney, and lower-than-expected prevalence in central and eastern Sydney. In fully adjusted spatial models, prevalence of overweight and obesity was 6% and 11% lower in medium-high versus low, and 10% and 15% lower in high versus low walkability postcodes, respectively. Postal area walkability explained approximately 20% and 9% of the excess spatial variation in overweight and obesity that remained after accounting for other individual- and area-level factors. These findings provide support for the potential of area-level walkability indexes to inform, benchmark and monitor regional plans aimed at targeted approaches to reducing population-levels of high body mass through environmental interventions. Future research should consider potential confounding due to neighbourhood self-selection on area-level walkability relations.
Social Capital and Mental Health in Rural and Urban China: A Composite Hypothesis Approach
Authors: Lin Xiaoming , Lu Ruodan , Guo Liang , Liu Bing
Published: February 2019

The objective of this study is to follow the composite theory approach to analyze the effect of social capital on self-rated mental health in rural and urban China. Our nationally representative sample includes 10,968 respondents from 130 county-level communities. Two-level random-coefficient linear regressions, which model individual and community variations in subjective mental health, were estimated by taking the hierarchical structure of the dataset into account. We found that a significant proportion of the total variations in self-rated mental health were explained at the community level. We also found an association between low contextual civic trust and poor self-rated mental health after adjusting for individual social capital and individual socioeconomic-demographic variables. The study also revealed that: (1) in rural areas a positive relationship between civic and political trust and mental health existed both at the individual and the community level, respectively; and (2) in urban areas, only political trust at the individual level contributed to better mental health. In addition, the individual and community level political participation exhibited a positive impact on mental health measures in both rural and urban China. The individual level civic participation was positively associated to the outcome variable. However, the community-level civic participation seemed to negatively impact mental health in urban area. Our findings emphasize the importance of both individual and community-level healthcare interventions in China. Finally, this study also found that human capital covariates remained important predictors of self-rated mental health status even after controlling social capital both at individual and community levels. This study suggested that the composite thesis could provide a more convincing narrative than other theories in explaining the effects of both human and social capital on health.
Parenting and Future Anxiety: The Impact of Having a Child with Developmental Disabilities
Authors: Bujnowska Anna M. , Rodríguez Celestino , García Trinidad , Areces Débora , Marsh Nigel V.
Published: February 2019

This study examined differences in future anxiety (FA) among mothers and fathers of children with and without developmental disabilities (DD), and it also analyzed differences in FA within the group of parents of children with DD taking into consideration parent-related factors and child-related factors. A group of 167 parents of children with DD were compared to a group of 103 parents of children with typical development. The group with DD included children with autism spectrum disorders, sensory disorders, and intellectual disability. Parents completed the Future Anxiety Scale-FAS1. Mothers of children with DD had a higher general level of FA than fathers of children with and without DD. Mothers of children with DD reported higher anxiety about their future health and the meaning of their future life than fathers of children with DD. For parents of children with DD, those with lower education, male children, and older children reported higher FA. The group at risk of highest general FA are mothers of children with DD, especially those without a professional career. Similarly, parents of teenagers and/or sons with DD are at increased risk of FA.
Spatio-Temporal Analysis of Infectious Diseases
Authors: López-Quílez Antonio
Published: February 2019

Epidemiological research on the pathogenesis, diagnosis, and treatment of infectious diseases is a broad field of study with renewed validity in the face of social changes and new threats [...]
Migrant Workers from the Eastern-Mediterranean Region and Occupational Injuries: A Retrospective Database-Based Analysis from North-Eastern Italy
Authors: Riccò Matteo , Garbarino Sergio , Bragazzi Nicola Luigi
Published: February 2019

The month of Ramadan is the ninth month of the Islamic lunar calendar, and, according to the Islamic tradition, it coincides with the month when the Noble Koran/Qur’an began to be revealed. In recent years, concerns about the potentially negative health effects of Ramadan fasting and the risks of work-related injuries have increased in Western European (EURO) countries. In the present study, we performed a retrospective database-based analysis assessing the impact of Ramadan fasting on occupational injuries (OIs) in North-Eastern Italy among migrant workers from the Eastern-Mediterranean Region (EMRO). Our results suggest that EMRO workers exhibit a significantly increased risk for OIs during Ramadan in periods characterized by heat-waves, while their frequency was somehow reduced for days associated with Ramadan characterized by increased but not extreme temperatures. However, these results may be attributable to an explanatory causation in the specific differences between EMRO and EURO workers in the job tasks performed at the workplace. Not coincidentally, no significant differences were found regarding industrial settings, mechanisms of OIs and final prognosis. Despite the obvious practical implications for health decision- and policy-makers, due to the limitations of the present investigation, further studies are warranted.
An Intuitionistic Fuzzy Similarity Approach for Clustering Analysis of Polygons
Authors: Chen Zhanlong , Ma Xiaochuan , Wu Liang , Xie Zhong
Published: February 2019

Accurate and reasonable clustering of spatial data results facilitates the exploration of patterns and spatial association rules. Although a broad range of research has focused on the clustering of spatial data, only a few studies have conducted a deeper exploration into the similarity approach mechanism for clustering polygons, thereby limiting the development of spatial clustering. In this study, we propose a novel fuzzy similarity approach for spatial clustering, called Extend Intuitionistic Fuzzy Set-Interpolation Boolean Algebra (EIFS-IBA). When discovering polygon clustering patterns by spatial clustering, this method expresses the similarities between polygons and adjacent graph models. Shape-, orientation-, and size-related properties of a single polygon are first extracted, and are used as indices for measuring similarities between polygons. We then transform the extracted properties into a fuzzy format through normalization and fuzzification. Finally, the similarity graph containing the neighborhood relationship between polygons is acquired, allowing for clustering using the proposed adjacency graph model. In this paper, we clustered polygons in Staten Island, United States. The visual result and two evaluation criteria demonstrated that the EIFS-IBA similarity approach is more expressive compared to the conventional similarity (ConS) approach, generating a clustering result more consistent with human cognition.
Materials for Photovoltaics: State of Art and Recent Developments
Authors: Luceño-Sánchez José Antonio , Díez-Pascual Ana María , Peña Capilla Rafael
Published: February 2019

In recent years, photovoltaic cell technology has grown extraordinarily as a sustainable source of energy, as a consequence of the increasing concern over the impact of fossil fuel-based energy on global warming and climate change. The different photovoltaic cells developed up to date can be classified into four main categories called generations (GEN), and the current market is mainly covered by the first two GEN. The 1GEN (mono or polycrystalline silicon cells and gallium arsenide) comprises well-known medium/low cost technologies that lead to moderate yields. The 2GEN (thin-film technologies) includes devices that have lower efficiency albeit are cheaper to manufacture. The 3GEN presents the use of novel materials, as well as a great variability of designs, and comprises expensive but very efficient cells. The 4GEN, also known as “inorganics-in-organics”, combines the low cost/flexibility of polymer thin films with the stability of novel inorganic nanostructures (i.e., metal nanoparticles and metal oxides) with organic-based nanomaterials (i.e., carbon nanotubes, graphene and its derivatives), and are currently under investigation. The main goal of this review is to show the current state of art on photovoltaic cell technology in terms of the materials used for the manufacture, efficiency and production costs. A comprehensive comparative analysis of the four generations is performed, including the device architectures, their advantages and limitations. Special emphasis is placed on the 4GEN, where the diverse roles of the organic and nano-components are discussed. Finally, conclusions and future perspectives are summarized.
BGFE: A Deep Learning Model for ncRNA-Protein Interaction Predictions Based on Improved Sequence Information
Authors: Zhan Zhao-Hui , Jia Li-Na , Zhou Yong , Li Li-Ping , Yi Hai-Cheng
Published: February 2019

The interactions between ncRNAs and proteins are critical for regulating various cellular processes in organisms, such as gene expression regulations. However, due to limitations, including financial and material consumptions in recent experimental methods for predicting ncRNA and protein interactions, it is essential to propose an innovative and practical approach with convincing performance of prediction accuracy. In this study, based on the protein sequences from a biological perspective, we put forward an effective deep learning method, named BGFE, to predict ncRNA and protein interactions. Protein sequences are represented by bi-gram probability feature extraction method from Position Specific Scoring Matrix (PSSM), and for ncRNA sequences, k-mers sparse matrices are employed to represent them. Furthermore, to extract hidden high-level feature information, a stacked auto-encoder network is employed with the stacked ensemble integration strategy. We evaluate the performance of the proposed method by using three datasets and a five-fold cross-validation after classifying the features through the random forest classifier. The experimental results clearly demonstrate the effectiveness and the prediction accuracy of our approach. In general, the proposed method is helpful for ncRNA and protein interacting predictions and it provides some serviceable guidance in future biological research.
Genome-Wide Detection of Major and Epistatic Effect QTLs for Seed Protein and Oil Content in Soybean Under Multiple Environments Using High-Density Bin Map
Authors: Karikari Benjamin , Li Shuguang , Bhat Javaid Akhter , Cao Yongce , Kong Jiejie , Yang Jiayin , Gai Junyi , Zhao Tuanjie
Published: February 2019

Seed protein and oil content are the two important traits determining the quality and value of soybean. Development of improved cultivars requires detailed understanding of the genetic basis underlying the trait of interest. However, it is prerequisite to have a high-density linkage map for precisely mapping genomic regions, and therefore the present study used high-density genetic map containing 2267 recombination bin markers distributed on 20 chromosomes and spanned 2453.79 cM with an average distance of 1.08 cM between markers using restriction-site-associated DNA sequencing (RAD-seq) approach. A recombinant inbred line (RIL) population of 104 lines derived from a cross between Linhefenqingdou and Meng 8206 cultivars was evaluated in six different environments to identify main- and epistatic-effect quantitative trait loci (QTLs)as well as their interaction with environments. A total of 44 main-effect QTLs for protein and oil content were found to be distributed on 17 chromosomes, and 15 novel QTL were identified for the first time. Out of these QTLs, four were major and stable QTLs, viz., qPro-7-1, qOil-8-3, qOil-10-2 and qOil-10-4, detected in at least two environments plus combined environment with R2 values >10%. Within the physical intervals of these four QTLs, 111 candidate genes were screened for their direct or indirect involvement in seed protein and oil biosynthesis/metabolism processes based on gene ontology and annotation information. Based on RNA sequencing (RNA-seq) data analysis, 15 of the 111 genes were highly expressed during seed development stage and root nodules that might be considered as the potential candidate genes. Seven QTLs associated with protein and oil content exhibited significant additive and additive × environment interaction effects, and environment-independent QTLs revealed higher additive effects. Moreover, three digenic epistatic QTLs pairs were identified, and no main-effect QTLs showed epistasis. In conclusion, the use of a high-density map identified closely linked flanking markers, provided better understanding of genetic architecture and candidate gene information, and revealed the scope available for improvement of soybean quality through marker assisted selection (MAS).
Ginseng Berry Extract Rich in Phenolic Compounds Attenuates Oxidative Stress but not Cardiac Remodeling post Myocardial Infarction
Authors: Parikh Mihir , Raj Pema , Yu Liping , Stebbing Jo-Ann , Prashar Suvira , Petkau Jay , Tappia Paramjit , Pierce Grant , Siow Yaw , Brown Dan , Blewett Heather , Netticadan Thomas
Published: February 2019

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague–Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.
Differential Involvement of Autophagy and Apoptosis in Response to Chemoendocrine and Endocrine Therapy in Breast Cancer: JBCRG-07TR
Authors: Ueno Takayuki , Masuda Norikazu , Kamigaki Shunji , Morimoto Takashi , Saji Shigehira , Imoto Shigeru , Sasano Hironobu , Toi Masakazu
Published: February 2019

Endocrine therapy is an essential component in the curative treatment of hormone receptor (HR)-positive breast cancer. To improve treatment efficacy, the addition of metronomic chemotherapy has been tested and shown to improve therapeutic effects. To better understand cellular reactions to metronomic chemoendocrine therapy, we studied autophagy-related markers, beclin 1 and LC3, and apoptosis-related markers, TUNEL and M30, in pre- and post-treatment cancer tissues from a multicenter neoadjuvant trial, JBCRG-07, in which oral cyclophosphamide plus letrozole were administered to postmenopausal patients with HR-positive breast cancer. Changes in the levels of markers were compared with those following neoadjuvant endocrine therapy according to clinical response. Apoptosis, in addition to autophagy-related markers, increased following metronomic chemoendocrine therapy and such increases were associated with clinical response. By contrast, following endocrine therapy, the levels of apoptosis-related markers did not increase regardless of clinical response, whereas the levels of autophagy-related markers increased. Furthermore, levels of the apoptosis-related marker, M30, decreased in responders of endocrine therapy, suggesting that the induction of apoptosis by metronomic chemoendocrine therapy was involved in the improved clinical outcome compared with endocrine therapy. In conclusion, metronomic chemoendocrine therapy induced a different cellular reaction from that of endocrine therapy, including the induction of apoptosis, which is likely to contribute to improved efficacy compared with endocrine therapy alone.
The Proteomic Analysis of Maize Endosperm Protein Enriched by Phos-tagtm Reveals the Phosphorylation of Brittle-2 Subunit of ADP-Glc Pyrophosphorylase in Starch Biosynthesis Process
Authors: Yu Guowu , Lv Yanan , Shen Leiyang , Wang Yongbin , Qing Yun , Wu Nan , Li Yangping , Huang Huanhuan , Zhang Na , Liu Yinghong , Hu Yufeng , Liu Hanmei , Zhang Junjie , Huang Yubi
Published: February 2019

AGPase catalyzes a key rate-limiting step that converts ATP and Glc-1-p into ADP-glucose and diphosphate in maize starch biosynthesis. Previous studies suggest that AGPase is modulated by redox, thermal and allosteric regulation. However, the phosphorylation of AGPase is unclear in the kernel starch biosynthesis process. Phos-tagTM technology is a novel method using phos-tagTM agarose beads for separation, purification, and detection of phosphorylated proteins. Here we identified phos-tagTM agarose binding proteins from maize endosperm. Results showed a total of 1733 proteins identified from 10,678 distinct peptides. Interestingly, a total of 21 unique peptides for AGPase sub-unit Brittle-2 (Bt2) were identified. Bt2 was demonstrated by immunoblot when enriched maize endosperm protein with phos-tagTM agarose was in different pollination stages. In contrast, Bt2 would lose binding to phos-tagTM when samples were treated with alkaline phosphatase (ALP). Furthermore, Bt2 could be detected by Pro-Q diamond staining specifically for phosphorylated protein. We further identified the phosphorylation sites of Bt2 at Ser10, Thr451, and Thr462 by iTRAQ. In addition, dephosphorylation of Bt2 decreased the activity of AGPase in the native gel assay through ALP treatment. Taking together, these results strongly suggest that the phosphorylation of AGPase may be a new model to regulate AGPase activity in the starch biosynthesis process.
Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity
Authors: Benkaidali Lydia , André François , Moroy Gautier , Tangour Bahoueddine , Maurel François , Petitjean Michel
Published: February 2019

We computed the network of channels of the 3A4 isoform of the cytochrome P450 (CYP) on the basis of 16 crystal structures extracted from the Protein Data Bank (PDB). The calculations were performed with version 2 of the CCCPP software that we developed for this research project. We identified the minimal cost paths (MCPs) output by CCCPP as probable ways to access to the buried active site. The algorithm of calculation of the MCPs is presented in this paper, with its original method of visualization of the channels. We found that these MCPs constitute four major channels in CYP3A4. Among the many channels proposed by Cojocaru et al. in 2007, we found that only four of them open in 3A4. We provide a refined description of these channels together with associated quantitative data.
FTIR and Raman Spectroscopy-Based Biochemical Profiling Reflects Genomic Diversity of Clinical Candida Isolates That May Be Useful for Diagnosis and Targeted Therapy of Candidiasis
Authors: Potocki Leszek , Depciuch Joanna , Kuna Ewelina , Worek Mariusz , Lewinska Anna , Wnuk Maciej
Published: February 2019

Despite the fact that Candida albicans is documented to be the main cause of human candidiasis, non-C. albicans Candida (NCAC) species, such as Candida glabrata and Candida tropicalis, are also suggested to be implicated in the etiopathogenesis of opportunistic fungal infections. As biology, epidemiology, pathogenicity, and antifungal resistance of NCAC species may be affected as a result of genomic diversity and plasticity, rapid and unambiguous identification of Candida species in clinical samples is essential for proper diagnosis and therapy. In the present study, 25 clinical isolates of C. albicans, C. glabrata, and C. tropicalis species were characterized in terms of their karyotype patterns, DNA content, and biochemical features. Fourier transform infrared (FTIR) spectra- and Raman spectra-based molecular fingerprints corresponded to the diversity of chromosomal traits and DNA levels that provided correct species identification. Moreover, Raman spectroscopy was documented to be useful for the evaluation of ergosterol content that may be associated with azole resistance. Taken together, we found that vibrational spectroscopy-based biochemical profiling reflects the variability of chromosome patterns and DNA content of clinical Candida species isolates and may facilitate the diagnosis and targeted therapy of candidiasis.
Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway
Authors: Dkhil Mohamed A. , Abdel Moneim Ahmed E. , Hafez Taghreed A. , Mubaraki Murad A. , Mohamed Walid F. , Thagfan Felwa A. , Al-Quraishy Saleh
Published: February 2019

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.
Transcriptomic Analysis for Indica and Japonica Rice Varieties under Aluminum Toxicity
Authors: Zhang Peng , Ding Zhuoran , Zhong Zhengzheng , Tong Hanhua
Published: February 2019

Aluminum (Al) at high concentrations inhibits root growth, damage root systems, and causes significant reductions in rice yields. Indica and Japonica rice have been cultivated in distinctly different ecological environments with different soil acidity levels; thus, they might have different mechanisms of Al-tolerance. In the present study, transcriptomic analysis in the root apex for Al-tolerance in the seedling stage was carried out within Al-tolerant and -sensitive varieties belonging to different subpopulations (i.e., Indica, Japonica, and mixed). We found that there were significant differences between the gene expression patterns of Indica Al-tolerant and Japonica Al-tolerant varieties, while the gene expression patterns of the Al-tolerant varieties in the mixed subgroup, which was inclined to Japonica, were similar to the Al-tolerant varieties in Japonica. Moreover, after further GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the transcriptomic data, we found that eight pathways, i.e., “Terpenoid backbone biosynthesis”, “Ribosome”, “Amino sugar and nucleotide sugar metabolism”, “Plant hormone signal transduction”, “TCA cycle”, “Synthesis and degradation of ketone bodies”, and “Butanoate metabolism” were found uniquely for Indica Al-tolerant varieties, while only one pathway (i.e., “Sulfur metabolism”) was found uniquely for Japonica Al-tolerant varieties. For Al-sensitive varieties, one identical pathway was found, both in Indica and Japonica. Three pathways were found uniquely in “Starch and sucrose metabolism”, “Metabolic pathway”, and “Amino sugar and nucleotide sugar metabolism”.
Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway
Authors: Chuang Yao-Chung , Chen Shang-Der , Hsu Chung-Yao , Chen Shu-Fang , Chen Nai-Ching , Jou Shuo-Bin
Published: February 2019

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known to regulate mitochondrial biogenesis. Resveratrol is present in a variety of plants, including the skin of grapes, blueberries, raspberries, mulberries, and peanuts. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, stroke, and epilepsy. This study examined the neuroprotective effect of resveratrol on mitochondrial biogenesis in the hippocampus following experimental status epilepticus. Kainic acid was microinjected into left hippocampal CA3 in Sprague Dawley rats to induce bilateral prolonged seizure activity. PGC-1α expression and related mitochondrial biogenesis were investigated. Amounts of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), cytochrome c oxidase 1 (COX1), and mitochondrial DNA (mtDNA) were measured to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis machinery after prolonged seizure were found in CA3. Resveratrol increased expression of PGC-1α, NRF1, and Tfam, NRF1 binding activity, COX1 level, and mtDNA amount. In addition, resveratrol reduced activated caspase-3 activity and attenuated neuronal cell damage in the hippocampus following status epilepticus. These results suggest that resveratrol plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1α signaling pathway.
Nonparametric Hyperbox Granular Computing Classification Algorithms
Authors: Liu Hongbing , Diao Xiaoyu , Guo Huaping
Published: February 2019

Parametric granular computing classification algorithms lead to difficulties in terms of parameter selection, the multiple performance times of algorithms, and increased algorithm complexity in comparison with nonparametric algorithms. We present nonparametric hyperbox granular computing classification algorithms (NPHBGrCs). Firstly, the granule has a hyperbox form, with the beginning point and the endpoint induced by any two vectors in N-dimensional (N-D) space. Secondly, the novel distance between the atomic hyperbox and the hyperbox granule is defined to determine the joining process between the atomic hyperbox and the hyperbox. Thirdly, classification problems are used to verify the designed NPHBGrC. The feasibility and superiority of NPHBGrC are demonstrated by the benchmark datasets compared with parametric algorithms such as HBGrC.
DFTHR: A Distributed Framework for Trajectory Similarity Query Based on HBase and Redis
Authors: Qin Jiwei , Ma Liangli , Liu Qing
Published: February 2019

In recent years positioning sensors have become ubiquitous, and there has been tremendous growth in the amount of trajectory data. It is a huge challenge to efficiently store and query massive trajectory data. Among the typical operation over trajectories, similarity query is an important yet complicated operator. It is useful in navigation systems, transportation optimizations, and so on. However, most existing studies have focused on handling the problem on a centralized system, while with a single machine it is difficult to satisfy the storage and processing requirements of mass data. A distributed framework for the similarity query of massive trajectory data is urgently needed. In this research, we propose DFTHR (distributed framework based on HBase and Redis) to support the similarity query using Hausdorff distance. DFTHR utilizes a segment-based data model with a number of optimizations for storing, indexing and pruning to ensure efficient querying capability. Furthermore, it adopts a bulk-based method to alleviate the cost for adjusting partitions, so that the incremental dataset can be efficiently supported. Additionally, DFTHR introduces a co-location-based distributed strategy and a node-locality-based parallel query algorithm to reduce the inter-worker cost overhead. Experiments show that DFTHR significantly outperforms other schemes.
Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
Authors: Grossfeld Paul , Nie Shuyi , Lin Lizhu , Wang Lu , Anderson Robert H.
Published: February 2019

Hypoplastic left heart syndrome occurs in up to 3% of all infants born with congenital heart disease and is a leading cause of death in this population. Although there is strong evidence for a genetic component, a specific genetic cause is only known in a small subset of patients, consistent with a multifactorial etiology for the syndrome. There is controversy surrounding the mechanisms underlying the syndrome, which is likely due, in part, to the phenotypic variability of the disease. The most commonly held view is that the “decreased” growth of the left ventricle is due to a decreased flow during a critical period of ventricular development. Research has also been hindered by what has been, up until now, a lack of genetically engineered animal models that faithfully reproduce the human disease. There is a growing body of evidence, nonetheless, indicating that the hypoplasia of the left ventricle is due to a primary defect in ventricular development. In this review, we discuss the evidence demonstrating that, at least for a subset of cases, the chamber hypoplasia is the consequence of hyperplasia of the contained cardiomyocytes. In this regard, hypoplastic left heart syndrome could be viewed as a neonatal form of cardiomyopathy. We also discuss the role of the endocardium in the development of the ventricular hypoplasia, which may provide a mechanistic basis for how impaired flow to the developing ventricle leads to the anatomical changes seen in the syndrome.
The Morphology, Structure, Mechanical Properties and Biocompatibility of Nanotubular Titania Coatings before and after Autoclaving Process
Authors: Radtke Aleksandra , Ehlert Michalina , Jędrzejewski Tomasz , Bartmański Michał
Published: February 2019

The autoclaving process is one of the sterilization procedures of implantable devices. Therefore, it is important to assess the impact of hot steam at high pressure on the morphology, structure, and properties of implants modified by nanocomposite coatings. In our works, we focused on studies on amorphous titania nanotubes produced by titanium alloy (Ti6Al4V) electrochemical oxidation in the potential range 5–60 V. Half of the samples were drying in argon stream at room temperature, and the second ones were drying additionally with the use of immersion in acetone and drying at 396 K. Samples were subjected to autoclaving and after sterilization they were structurally and morphologically characterized using Raman spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and scanning electron microscopy (SEM). They were characterized in terms of wettability, mechanical properties, and biocompatibility. Obtained results proved that the autoclaving of amorphous titania nanotube coatings produced at lower potentials (5–15 V) does not affect their morphology and structure regardless of the drying method before autoclaving. Nanotubular coatings produced using higher potentials (20–60 V) require removal of adsorbed water particles from their surface. Otherwise, autoclaving leads to the destruction of the architecture of nanotubular coatings, which is associated with the changing of their mechanical and biointegration properties.