bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Collective Histone State Dynamics on Epigenetic Landscape and Kinetics of Cell Reprogramming
Authors: Ashwin S. S. , Sasai Masaki 
Published: November 2015

AbstractCell reprogramming is a process of transitions from differentiated to pluripotent cell states via transient intermediate states. Within the epigenetic landscape framework, such a process is regarded as a sequence of transitions among basins on the landscape; therefore, theoretical construction of a model landscape which exhibits experimentally consistent dynamics can provide clues to understanding epigenetic mechanism of reprogramming. We propose a minimal gene-network model of the landscape, in which each gene is regulated by an integrated mechanism of transcription-factor binding/unbinding and the collective chemical modification of histones. We show that the slow collective variation of many histones around each gene locus alters topology of the landscape and significantly affects transition dynamics between basins. Differentiation and reprogramming follow different transition pathways on the calculated landscape, which should be verified experimentally via single-cell pursuit of the reprogramming process. Effects of modulation in collective histone state kinetics on transition dynamics and pathway are examined in search for an efficient protocol of reprogramming.
Influence of age on rat bone-marrow mesenchymal stem cells potential
Authors: Fafián-Labora J. , Fernández-Pernas P. , Fuentes I. , De Toro J. , Oreiro N. , Sangiao-Alvarellos S. , Mateos J. , Arufe M.C. 
Published: November 2015

AbstractMesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending.
Adipose tissue macrophages induce PPARγ-high FOXP3+ regulatory T cells
Authors: Onodera Toshiharu , Fukuhara Atsunori , Jang Myoung Ho , Shin Jihoon , Aoi Keita , Kikuta Junichi , Otsuki Michio , Ishii Masaru , Shimomura Iichiro 
Published: November 2015

AbstractNumerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear. Here, we revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose Tregs. ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. Furthermore, ATMs from obese mice prompted the differentiation of PPARγ low Tregs. Adoptive transfer of ATMs induced differentiation and proliferation of Tregs, whereas depletion of ATMs by clodronate-liposome resulted in reduction of adipose Tregs, in vivo. Deficiency of anti-inflammatory adipocytokine, Adipoq, resulted in small proportions of ATMs and adipose Tregs without alteration of other immune cells in vivo. Therefore, these data suggest that the abundance of Tregs in adipose tissue could be partly attributed to the ability of ATMs to induce PPARγ-expressing Tregs.
Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer
Authors: Gupta Shilpi , Kumar Prabhat , Kaur Harsimrut , Sharma Nishi , Saluja Daman , Bharti Alok C. , Das Bhudev C. 
Published: November 2015

AbstractTongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers.
Observed contrast changes in snow cover phenology in northern middle and high latitudes from 2001–2014
Authors: Chen Xiaona , Liang Shunlin , Cao Yunfeng , He Tao , Wang Dongdong 
Published: November 2015

AbstractQuantifying and attributing the phenological changes in snow cover are essential for meteorological, hydrological, ecological and societal implications. However, snow cover phenology changes have not been well documented. Evidence from multiple satellite and reanalysis data from 2001 to 2014 points out that the snow end date (De) advanced by 5.11 (±2.20) days in northern high latitudes (52–75°N) and was delayed by 3.28 (±2.59) days in northern mid-latitudes (32–52°N) at the 90% confidence level. Dominated by changes in De, snow duration days (Dd) was shorter in duration by 5.57 (±2.55) days in high latitudes and longer by 9.74 (±2.58) days in mid-latitudes. Changes in De during the spring season were consistent with the spatiotemporal pattern of land surface albedo change. Decreased land surface temperature combined with increased precipitation in mid-latitudes and significantly increased land surface temperature in high latitudes, impacted by recent Pacific surface cooling, Arctic amplification and strengthening westerlies, result in contrasting changes in the Northern Hemisphere snow cover phenology. Changes in the snow cover phenology led to contrasting anomalies of snow radiative forcing, which is dominated by De and accounts for 51% of the total shortwave flux anomalies at the top of the atmosphere.
Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma
Authors: Azevedo Hátylas , Moreira-Filho Carlos Alberto 
Published: November 2015

AbstractBiological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.
Intestinal organoids for assessing nutrient transport, sensing and incretin secretion
Authors: Zietek Tamara , Rath Eva , Haller Dirk , Daniel Hannelore 
Published: November 2015

AbstractIntestinal nutrient transport and sensing are of emerging interest in research on obesity and diabetes and as drug targets. Appropriate in vitro models are lacking that allow both, studies on transport processes as well as sensing and subsequent incretin hormone secretion including intracellular signaling. We here demonstrate that murine small-intestinal organoids are the first in vitro model system enabling concurrent investigations of nutrient and drug transport, sensing and incretin hormone secretion as well as fluorescent live-cell imaging of intracellular signaling processes. By generating organoid cultures from wild type mice and animals lacking different nutrient transporters, we show that organoids preserve the main phenotypic features and functional characteristics of the intestine. This turns them into the best in vitro model currently available and opens new avenues for basic as well as medical research.
Indium-free, highly transparent, flexible Cu2O/Cu/Cu2O mesh electrodes for flexible touch screen panels
Authors: Kim Dong-Ju , Kim Hyo-Joong , Seo Ki-Won , Kim Ki-Hyun , Kim Tae-Wong , Kim Han-Ki 
Published: November 2015

AbstractWe report on an indium-free and cost-effective Cu2O/Cu/Cu2O multilayer mesh electrode grown by room temperature roll-to-roll sputtering as a viable alternative to ITO electrodes for the cost-effective production of large-area flexible touch screen panels (TSPs). By using a low resistivity metallic Cu interlayer and a patterned mesh structure, we obtained Cu2O/Cu/Cu2O multilayer mesh electrodes with a low sheet resistance of 15.1 Ohm/square and high optical transmittance of 89% as well as good mechanical flexibility. Outer/inner bending test results showed that the Cu2O/Cu/Cu2O mesh electrode had a mechanical flexibility superior to that of conventional ITO films. Using the diamond-patterned Cu2O/Cu/Cu2O multilayer mesh electrodes, we successfully demonstrated TSPS of the flexible film-film type and rigid glass-film-film type TSPs. The TSPs with Cu2O/Cu/Cu2O mesh electrode were used to perform zoom in/out functions and multi-touch writing, indicating that these electrodes are promising cost-efficient transparent electrodes to substitute for conventional ITO electrodes in large-area flexible TSPs.
Proteome analysis of male accessory gland secretions in oriental fruit flies reveals juvenile hormone-binding protein, suggesting impact on female reproduction
Authors: Wei Dong , Li Hui-Min , Tian Chuan-Bei , Smagghe Guy , Jia Fu-Xian , Jiang Hong-Bo , Dou Wei , Wang Jin-Jun 
Published: November 2015

AbstractIn insects, the accessory gland proteins (Acps) secreted by male accessory glands (MAGs) account for the majority of seminal fluids proteins. Mixed with sperm, they are transferred to the female at mating and so impact reproduction. In this project, we identified 2,927 proteins in the MAG secretions of the oriental fruit flyBactrocera dorsalis, an important agricultural pest worldwide, using LC-MS analysis and all sequences containing open reading frames were analyzed using signalP. In total, 90 Acps were identified. About one third (26) of these 90 Acps had a specific functional description, while the other two thirds (64) had no functional description including dozens of new classes of proteins. Hence, several of these novel Acps were abundant in the MAG secretions and we confirmed their MAG-specific expression by qPCR. Finally and interestingly, one of these novel proteins was functionally predicted as juvenile hormone-binding protein, suggesting the impact of Acps with reproductive events in the female. Our results will aid in the development of an experimental method to identify Acps in insects and in turn this information with new Acps inB. dorsaliswill pave the way of further exploration their function in reproduction and potential development as new insecticide targets.
Dendritic cells and macrophages neurally hard-wired in the lymph node
Authors: Wülfing Clemens , Günther Hauke S. 
Published: November 2015

AbstractThe neural hard-wired pathways in which the lymphoid organs are innervated by the nervous system is of special interest with respect to suggested afferent and sensory systems informing the central nervous system about the status of the immune system. Until today efferent also like afferent innervation seem to be unspecific, targeting many types of cells by affecting many cells at the same time. We for the first time show that antigen presenting cells (APC) are abundantly innervated in the T-cell enriched area, the subsinoidal layer and the cortical extrafollicular zone of lymph nodes in rats by a mesh of filamentous neurofilament positive structures originating from single nerve fibers and covering each single APC similar to a glass fishing float, so that we termed them “wired” APC (wAPC). These wAPC also found in humans seem to be restricted to the cell body, not to follow membranous extensions, they may be dynamic and receptive as MAP2 is expressed and axonal growth cones can be detected and they probably lack vesicular activity through missing synaptophysin expression. The specific innervation targeting single cells which show a distribution divided in several areas in one lymph node suggests a form of topographically organized afferent sensory system.
Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis
Authors: Sathyapalan T. , David R. , Gooderham N. J. , Atkin S. L. 
Published: November 2015

AbstractMicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules that regulate gene expression. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS). The objective was to determine if miRNA-93 and miRNA-223 are differentially expressed in the circulation of women with PCOS compared to age matched women. A case–control study comparing women with PCOS (n = 25) to age and weight matched controls (n = 24) without PCOS was performed. MiRNA-93 and miRNA-223 were determined by total RNA reverse transcription. Both miRNA-93 and miRNA-223 were significantly increased relative to the control group (p < 0.01, p = 0.029 respectively). In both groups there was no correlation of either miRNA-93 or miRNA-223 with insulin, HOMA-IR, HOMA-β or testosterone levels. The area under the receiver operator characteristic curve for miR-223 and miR-93 was 0.66 and 0.72 respectively, suggesting miR-93 is a more efficient biomarker than miR-223 for diagnosis of PCOS. The combination of the two miRNAs together, tested using multiple logistic regression analysis, did not improve the diagnostic potential. In conclusion, circulating miRNA-93 and miRNA-223 were higher in women with PCOS compared to age and weight matched controls independent of insulin resistance and testosterone levels and miR-93 may represent a novel diagnostic biomarker for PCOS.
DNA methylation mediated silencing of microRNA-145 is a potential prognostic marker in patients with lung adenocarcinoma
Authors: Xia Wenjie , Chen Qiang , Wang Jie , Mao Qixing , Dong Gaochao , Shi Run , Zheng YanYan , Xu Lin , Jiang Feng 
Published: November 2015

AbstractThe molecular mechanism of down-regulated microRNA-145 (miR-145) expression in lung adenocarcinoma (LAC) remains largely unknown. We hypothesized that aberrant hyper-methylation of the CpG sites silenced the expression of miR-145 in LAC. In consideration of its pivotal role in LAC development and progression, we also evaluated the clinical utility of miR-145 as a prognostic marker. We assessed the DNA methylation status of the miR-145 promoter region in 20 pairs of LAC and the matched non-tumor specimens. We subsequently applied our own LAC tissue microarray containing 92 pairs of tumor and non-tumor tissues with long time follow-up records to evaluate whether miR-145 is a potential prognostic marker in LAC. The Sequenom EpiTYPER MassArray analysis showed that miR-145 was down-regulated in human LAC tissues accompanied by increased DNA methylation of its upstream region, which was further validated by the data from TCGA database. Significance was observed between miR-145 expression and clinic-pathologic parameters. Univariate and multivariate analysis revealed that miR-145 expression level was an independent risk factor for both OS and DFS in LAC patients. Taken together, DNA hyper-methylation in the miR-145 promoter region reduced its expression in LAC and miR-145 expression level might serve as a novel prognostic biomarker.
Collective effects of common SNPs in foraging decisions in Caenorhabditis elegans and an integrative method of identification of candidate genes
Authors: Zhu Zuobin , Lu Qing , Wang Junjing , Huang Shi 
Published: November 2015

AbstractOptimal foraging decision is a quantitative flexible behavior, which describes the time at which animals choose to abandon a depleting food supply. The total minor allele content (MAC) in an individual has been shown to correlate with quantitative variations in complex traits. We have studied the role of MAC in the decision to leave a food lawn in recombinant inbred advanced intercross lines (RIAILs) of Caenorhabditis elegans. We found a strong link between MAC and the food lawn leaving rates (Spearman r = 0.4, P = 0.005). We identified 28 genes of unknown functions whose expression levels correlated with both MAC and leaving rates. When examined by RNAi experiments, 8 of 10 tested among the 28 affected leaving rates, whereas only 2 of 9 did among genes that were only associated with leaving rates but not MAC (8/10 vs 2/9, P < 0.05). The results establish a link between MAC and the foraging behavior and identify 8 genes that may play a role in linking MAC with the quantitative nature of the trait. The method of correlations with both MAC and traits may find broad applications in high efficiency identification of target genes for other complex traits in model organisms and humans.
Responses of the Hybrid between Sphagneticola trilobata and Sphagneticola calendulacea to Low Temperature and Weak Light Characteristic in South China
Authors: Sun Zhongyu , Chen Yanqiao , Schaefer Valentin , Liang Huimiao , Li Weihua , Huang Shengqin , Peng Changlian 
Published: November 2015

AbstractHybridization between exotic and native species is of great interest to evolutionary biologists and ecologists because it usually shows a quick evolution of species and invasiveness. It has been reported that such hybridization frequently increases the adaptation and aggressiveness of the new hybrids. A hybrid between invasiveSphagneticola trilobataand its native congenerS. calendulaceawas recently found in subtropical China. S. calendulaceahas a significantly higher tolerance to low temperature and weak light stress thanS. trilobataand its range includes both tropical and temperate regions. This study examined how the tolerance of the new hybrid to low temperature and weak light conditions (LTWL), expanded its geographical range. All changes of phenotype, gas exchange parameters, chlorophyll fluorescence parameters, contents of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) and peroxidase (POD) indicated that hybridization slightly catalyzed the tolerance of the hybrid to LTWL condition and the responses of the hybrid were more similar with their invasive parent. The results demonstrate that the current hybrid populations may not expand their geographical distribution ranges in a short period, but the distribution of the backcrossed generations is still uncertain. The threat of the hybrid to its native parent in subtropical region should be concerned.
Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis
Authors: Katayama Akihiro , Nakatsuka Atsuko , Eguchi Jun , Murakami Kazutoshi , Teshigawara Sanae , Kanzaki Motoko , Nunoue Tomokazu , Hida Kazuyuki , Wada Nozomu , Yasunaka Tetsuya , Ikeda Fusao , Takaki Akinobu , Yamamoto Kazuhide , Kiyonari Hiroshi , Makino Hirofumi , Wada Jun 
Published: November 2015

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity.
Prenatal exposure to recreational drugs affects global motion perception in preschool children
Authors: Chakraborty Arijit , Anstice Nicola S. , Jacobs Robert J. , LaGasse Linda L. , Lester Barry M. , Wouldes Trecia A. , Thompson Benjamin 
Published: November 2015

AbstractPrenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.5-year-old children who had been exposed to different combinations of methamphetamine, alcohol, nicotine and marijuana prior to birth and 25 unexposed children. Self-reported drug use by the mothers was verified by meconium analysis. We found that global motion perception was impaired by prenatal exposure to alcohol and improved significantly by exposure to marijuana. Exposure to both drugs prenatally had no effect. Other visual functions such as habitual visual acuity and stereoacuity were not affected by drug exposure. Prenatal exposure to methamphetamine did not influence visual function. Our results demonstrate that prenatal drug exposure can influence a behavioural measure of visual development, but that the effects are dependent on the specific drugs used during pregnancy.