1,150 research outputs found

    Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics

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    Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively. Transcriptome data of cells treated with CKI or 5-Fluorouracil (5-FU) for 24 and 48 hours were subsequently acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.Zhipeng Qu, Jian Cui, Yuka Harata-Lee, Thazin Nwe Aung, Qianjin Feng, Joy M. Raison, Robert Daniel Kortschak, David L. Adelso

    Land systems as surrogates for biodiversity in conservation planning

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    Environmental surrogates (land classes) for the distribution of biodiversity are increasingly being used for conservation planning. However; data that demonstrate coincident patterns in land classes and biodiversity are limited. We ask the overall question, "Are land systems effective surrogates for the spatial configuration of biodiversity for conservation planning?" and we address three specific questions: (1) Do different land systems represent different biological assemblages.? (2) Do biological assemblages on the same land system remain similar with increasing geographic separation? and (3) Do biological assemblages on the same land system remain similar with increasing land system isolation? Vascular plants, invertebrates, and microbiota were surveyed from 24 sites in four land systems in and northwest New South Wales, Australia. Within each land system, sites were located to give a hierarchy of inter-site distances, and land systems were classified as either "low isolation" (large and continuous) or "high isolation" (small patches interspersed among other land systems). Each type of land system supported components of biodiversity either not found, or found infrequently, on other land systems, suggesting that land systems function as surrogates for biodiversity, and that conservation-area networks representing land-system diversity will also represent biological diversity. However, the majority of taxa were found on more than one land-system type, suggesting that a large proportion of the plant, arthropod, and microbial biodiversity may be characterized by widespread species with low fidelity to particular land systems. Significant relationships between geographic distance among sites and differences among assemblages were revealed for all taxa except the microbiota. Therefore, as sites on the same land system were located farther apart, the assemblages at those sites became more different. This finding strongly suggests that conservation planning based on land-system diversity should also sample the geographic range occupied by each land system. Land-system isolation was not revealed to be a significant Source of variation in assemblage composition. Our research finds support for environmental surrogates for biodiversity in conservation planning, specifically the use of land systems and similarly derived land classifications. However, the need for explicit modeling of geographic distance in conservation planning is clearly indicated

    In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

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    Available online 17 February 2016SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.King-Hwa Ling, Peter J. Brautigan, Sarah Moore, Rachel Fraser, Melody Pui-Yee Leong, Jia-Wen Leong, Shahidee Zainal Abidin, Han-Chung Lee, Pike-See Cheah, Joy M. Raison, Milena Babic, Young Kyung Lee, Tasman Daish, Deidre M. Mattiske, Jeffrey R. Mann, David L. Adelson, Paul Q. Thomas, Christopher N. Hahn, Hamish S.Scot

    Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

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    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons

    Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

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    Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3

    DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP

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    Transcriptional differences in interleukin-11 (IL11) after antidepressant treatment have been found to correspond to clinical response in major depressive disorder (MDD) patients. Expression differences were partly mediated by a single-nucleotide polymorphism (rs1126757), identified as a predictor of antidepressant response as part of a genome-wide association study. Here we attempt to identify whether DNA methylation, another baseline factor known to affect transcription factor binding, might also predict antidepressant response, using samples collected from the Genome-based Therapeutic Drugs for Depression project (GENDEP). DNA samples from 113 MDD individuals from the GENDEP project, who were treated with either escitalopram (n=80) or nortriptyline (n=33) for 12 weeks, were randomly selected. Percentage change in Montgomery-� sberg Depression Rating Scale scores between baseline and week 12 were utilized as our measure of antidepressant response. The Sequenom EpiTYPER platform was used to assess DNA methylation across the only CpG island located in the IL11 gene. Regression analyses were then used to explore the relationship between CpG unit methylation and antidepressant response. We identified a CpG unit predictor of general antidepressant response, a drug by CpG unit interaction predictor of response, and a CpG unit by rs1126757 interaction predictor of antidepressant response. The current study is the first to investigate the potential utility of pharmaco-epigenetic biomarkers for the prediction of antidepressant response. Our results suggest that DNA methylation in IL11 might be useful in identifying those patients likely to respond to antidepressants, and if so, the best drug suited to each individual

    <i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

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    Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

    Salivary Cortisol and Binge Eating Disorder in Obese Women After Surgery for Morbid Obesity

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    Contains fulltext : 77127.pdf (publisher's version ) (Closed access)Background Binge eating episodes characterized by loss of control are hypothesized to be accompanied by changes in hypothalamic pituitary adrenal (HPA) axis functioning. Cortisol is an end product of this neuroendocrine stress system. Purpose The aim of this study was to examine the cortisol levels and the awakening cortisol response (ACR) in obese persons showing binge eating after surgery for morbid obesity. Method Sixteen obese women with binge eating disorder (BED) and 18 obese women without BED participated in the study. Means±SD: age 43 ± 15, body mass index 40 ± 8. Salivary cortisol, anthropometric assessments, and the eating disorder examination interview were taken. Results Women with BED showed a significantly lower waist-to-hip ratio and cortisol levels during the day than women without BED, whereas the ACR did not differ. Conclusion Our cross-sectional study in a small sample generates the hypothesis that neuroendocrine regulation differs between obese women with and without BED after obesity surgery. This finding needs replication in future studies that should also examine the causal direction of the observed association
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