69 research outputs found

    Obesity of women in Jordan - Prevalence and associated factors : making a case for a comprehensive obesity policy

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    This paper analyses the current burden of obesity in the female population of Jordan on a national scale and examines the factors associated with it. Demographics and Health Surveys (DHS) were used for the years 2002, 2007 and 2009 covering a total of 23,197 women, 15-49 years of age, and variables including body mass index, age, governorate, educational level, marital status and wealth index, among others were investigated. The overall prevalence of obesity (body mass index, BMI ? 30) in Jordanian women was found to be 26.3 percent in 2002, 19.7 percent in 2007 and 28.2 percent in 2009. Multivariate analysis demonstrated that being obese was significantly associated with increasing age, being married and having only primary education. Apart from age, the strength of these associations decreased from 2002 to 2009 which could point to a generalisation obesity epidemic, for all population groups. This paper contributes to the increasing research on obesity in Jordan, and confirms many findings of smaller studies, by including a larger sample size and greater geographic coverage, on a national scale. The contextual policy analysis reveals that the public health efforts of the Jordanian government are relatively limited in this area, and concludes by trying to make a case for a more comprehensive approach in order to moderate the health impact of obesity in Jordan

    Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

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    BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes. METHODS: We performed RNA sequencing and DNA methylation (Illumina Infinium microarray) of 40 diagnosis and 42 relapse samples from 45 BCP-ALL patients in a German cohort and quantified lncRNA expression. Unsupervised clustering was applied to ascertain and confirm that the lncRNA-based classification of the BCP-ALL molecular subtypes is present in both our cohort and an independent validation cohort of 47 patients. A differential expression and differential methylation analysis was applied to determine the subtype-specific, relapse-specific, and differentially methylated lncRNAs. Potential functions of subtype-specific lncRNAs were determined by using co-expression-based analysis on nearby (cis) and distally (trans) located protein-coding genes. RESULTS: Using an integrative Bioinformatics analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCP-ALL subtype-specific and 942 relapse-specific lncRNAs and the methylation profile of three subtypes of BCP-ALL. The 1235 subtype-specific lncRNA signature represented a similar classification of the molecular subtypes of BCP-ALL in the independent validation cohort. We identified a strong correlation between the DUX4-specific lncRNAs and genes involved in the activation of TGF-β and Hippo signaling pathways. Similarly, Ph-like-specific lncRNAs were correlated with genes involved in the activation of PI3K-AKT, mTOR, and JAK-STAT signaling pathways. Interestingly, the relapse-specific lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we found 23 promoter methylated lncRNAs epigenetically facilitating their expression levels. CONCLUSION: Here, we describe a set of subtype-specific and relapse-specific lncRNAs from three major BCP-ALL subtypes and define their potential functions and epigenetic regulation. The subtype-specific lncRNAs are reproducible and can effectively stratify BCP-ALL subtypes. Our data uncover the diverse mechanism of action of lncRNAs in BCP-ALL subtypes defining which lncRNAs are involved in the pathogenesis of disease and are relevant for the stratification of BCP-ALL subtypes

    Epigenetic Silencing of Spermatocyte-Specific and Neuronal Genes by SUMO Modification of the Transcription Factor Sp3

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    SUMO modification of transcription factors is linked to repression of transcription. The physiological significance of SUMO attachment to a particular transcriptional regulator, however, is largely unknown. We have employed the ubiquitously expressed murine transcription factor Sp3 to analyze the role of SUMOylation in vivo. We generated mice and mouse embryonic fibroblasts (MEFs) carrying a subtle point mutation in the SUMO attachment sequence of Sp3 (IKEE553D mutation). The E553D mutation impedes SUMOylation of Sp3 at K551 in vivo, without affecting Sp3 protein levels. Expression profiling revealed that spermatocyte-specific genes, such as Dmc1 and Dnahc8, and neuronal genes, including Paqr6, Rims3, and Robo3, are de-repressed in non-testicular and extra-neuronal mouse tissues and in mouse embryonic fibroblasts expressing the SUMOylation-deficient Sp3E553D mutant protein. Chromatin immunoprecipitation experiments show that transcriptional de-repression of these genes is accompanied by the loss of repressive heterochromatic marks such as H3K9 and H4K20 tri-methylation and impaired recruitment of repressive chromatin-modifying enzymes. Finally, analysis of the DNA methylation state of the Dmc1, Paqr6, and Rims3 promoters by bisulfite sequencing revealed that these genes are highly methylated in Sp3wt MEFs but are unmethylated in Sp3E553D MEFs linking SUMOylation of Sp3 to tissue-specific CpG methylation. Our results establish SUMO conjugation to Sp3 as a molecular beacon for the assembly of repression machineries to maintain tissue-specific transcriptional gene silencing

    Event-Related Potentials Reveal Rapid Verification of Predicted Visual Input

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    Human information processing depends critically on continuous predictions about upcoming events, but the temporal convergence of expectancy-based top-down and input-driven bottom-up streams is poorly understood. We show that, during reading, event-related potentials differ between exposure to highly predictable and unpredictable words no later than 90 ms after visual input. This result suggests an extremely rapid comparison of expected and incoming visual information and gives an upper temporal bound for theories of top-down and bottom-up interactions in object recognition

    Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia

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    The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia..O. and T. Berg (BE 4198/1-1 and BE 4198/2-1) are supported by the Deutsche Forschungsgemeinschaft (DFG). K.S. is supported by a Leukemia and Lymphoma Society Scholar Award and by the National Cancer Institute (R01 CA140292). F.C. is supported by an EMBO long-term fellowship (1305-2015 and Marie Curie ActionsLTFCOFUND2013/GA-2013-609409). F.K. was supported by grants from Deutsche Krebshilfe (grant 109420; Max-Eder program), fellowship 2010/04 by the European Hematology Association, and by the DFG (SFB 1074, project A5). A.R. was supported by the DFG (SFB 1074, project A5) and the gender equality program by the DFG (SFB 1074, project Z2), a fellowship from the Canadian Institutes of Health Research, and the Baustein Startförderung Program of the Medical Faculty, Ulm University. Work in the Department of Haematology in Cambridge is supported by Bloodwise (grant ref. 13003), the Wellcome Trust (grant ref. 104710/Z/14/Z), the Medical Research Council (MC_PC_12009), the Kay Kendall Leukemia Fund (KKL952), the Cambridge NIHR Biomedical Research Center (NF-BR-0412-10321), the Cambridge Experimental Cancer Medicine Centre itself receives funding from NIHR (NF-EC-0412-10442), the Leukemia and Lymphoma Society of America (grant ref. 07037), and core support grants from the Wellcome Trust (100140/Z/12/Z and 097922/Z/11/Z) and MRC (MC_PC_12009)

    Obesity of women in Jordan - Prevalence and associated factors : making a case for a comprehensive obesity policy

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    This paper analyses the current burden of obesity in the female population of Jordan on a national scale and examines the factors associated with it. Demographics and Health Surveys (DHS) were used for the years 2002, 2007 and 2009 covering a total of 23,197 women, 15-49 years of age, and variables including body mass index, age, governorate, educational level, marital status and wealth index, among others were investigated. The overall prevalence of obesity (body mass index, BMI ? 30) in Jordanian women was found to be 26.3 percent in 2002, 19.7 percent in 2007 and 28.2 percent in 2009. Multivariate analysis demonstrated that being obese was significantly associated with increasing age, being married and having only primary education. Apart from age, the strength of these associations decreased from 2002 to 2009 which could point to a generalisation obesity epidemic, for all population groups. This paper contributes to the increasing research on obesity in Jordan, and confirms many findings of smaller studies, by including a larger sample size and greater geographic coverage, on a national scale. The contextual policy analysis reveals that the public health efforts of the Jordanian government are relatively limited in this area, and concludes by trying to make a case for a more comprehensive approach in order to moderate the health impact of obesity in Jordan

    Schallschalter: Photoschaltbare Reporter und Sensoren in der Optoakustik.

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    Optoacoustic imaging offers a unique combination of observation volume and achievable resolution in vivo. However, the use of transgene labeling agents has been impractical because their signal is low compared to the background of the tissue. Thus, detection was limited to large numbers of cells. We tackle this problem by using switchable agents — switching creates a signal modulation which allows to separate the labeled cells from the constant background — making it virtually invisible
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