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  • 1
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    The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Recommended Patient-Reported Core Set of Symptoms to Measure in Prostate Cancer Treatment Trials (2014)
    Oxford University Press
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    Publication Date: 2014-07-10
    Description: The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group’s process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Remote Sensing, Vol. 6, Pages 1739-1759: GIS-Based Roughness Derivation for Flood Simulations: A Comparison of Orthophotos, LiDAR and Crowdsourced Geodata (2014)
    MDPI Publishing
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    Publication Date: 2014-02-25
    Description: Natural disasters like floods are a worldwide phenomenon and a serious threat to mankind. Flood simulations are applications of disaster control, which are used for the development of appropriate flood protection. Adequate simulations require not only the geometry but also the roughness of the Earth’s surface, as well as the roughness of the objects hereon. Usually, the floodplain roughness is based on land use/land cover maps derived from orthophotos. This study analyses the applicability of roughness map derivation approaches for flood simulations based on different datasets: orthophotos, LiDAR data, official land use data, OpenStreetMap data and CORINE Land Cover data. Object-based image analysis is applied to orthophotos and LiDAR raster data in order to generate land cover maps, which enable a roughness parameterization. The vertical vegetation structure within the LiDAR point cloud is used to derive an additional floodplain roughness map. Further roughness maps are derived from official land use data, OpenStreetMap and CORINE Land Cover datasets. Six different flood simulations are applied based on one elevation data but with the different roughness maps. The results of the hydrodynamic–numerical models include information on flow velocity and water depth from which the additional attribute flood intensity is calculated of. The results based on roughness maps derived from LiDAR data and OpenStreetMap data are comparable, whereas the results of the other datasets differ significantly.
    Electronic ISSN: 2072-4292
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by MDPI Publishing
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  • 4
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    IJERPH, Vol. 11, Pages 7896-7917: The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies (2014)
    MDPI Publishing
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    Publication Date: 2014-08-07
    Description: The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.
    Print ISSN: 1661-7827
    Electronic ISSN: 1660-4601
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by MDPI Publishing
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  • 5
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    Energies, Vol. 11, Pages 645: Sucrose Is a Promising Feedstock for the Synthesis of the Platform Chemical Hydroxymethylfurfural (2018)
    MDPI Publishing
    In: Energies
    Details
    Publication Date: 2018-03-14
    Description: Energies, Vol. 11, Pages 645: Sucrose Is a Promising Feedstock for the Synthesis of the Platform Chemical Hydroxymethylfurfural Energies doi: 10.3390/en11030645 Authors: David Steinbach Andrea Kruse Jörg Sauer Philipp Vetter Hydroxymethylfurfural (HMF) has an outstanding position among bio-based platform chemicals, because high-value polymer precursors and fuel additives can be derived from HMF. Unfortunately, the large-scale industrial production of HMF is not yet realized. An open research question is the choice of hexose feedstock material. In this study, we used the highly available disaccharide sucrose for HMF synthesis. The conversion of sucrose was catalyzed by sulfuric acid in water media. Experiments were conducted at temperatures of 180, 200, and 220 °C with reaction times of 2–24 min. A carbon balance showed that the yield of unwanted side products rose strongly with temperature. We also developed a kinetic model for the conversion of sucrose, involving nine first-order reactions, to uncover the kinetics of the main reaction pathways. Within this model, HMF is produced exclusively via the dehydration of fructose. Glucose isomerizes slowly to fructose. Side products arise simultaneously from glucose, fructose, and HMF. A pathway from hexoses to xylose via reverse aldol reaction was also included in the model. We believe that sucrose is the ideal feedstock for large-scale production of HMF because it is more abundant than fructose, and easier to process than sugars obtained from lignocellulosic biomass.
    Electronic ISSN: 1996-1073
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by MDPI Publishing
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  • 6
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    Developmental regulation of N-terminal H2B methylation in Drosophila melanogaster (2012)
    Oxford University Press
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    Publication Date: 2012-02-28
    Description: Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo . Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other’s activity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Solving or resolving global tomographic models with spherical wavelets, and the scale and sparsity of seismic heterogeneity (2011)
    Oxford University Press
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    Publication Date: 2011-09-29
    Description: SUMMARY We propose a class of spherical wavelet bases for the analysis of geophysical models and for the tomographic inversion of global seismic data. Its multiresolution character allows for modelling with an effective spatial resolution that varies with position within the Earth. Our procedure is numerically efficient and can be implemented with parallel computing. We discuss two possible types of discrete wavelet transforms in the angular dimension of the cubed sphere. We describe benefits and drawbacks of these constructions and apply them to analyse the information in two published seismic wave speed models of the mantle, using the statistics of wavelet coefficients across scales. The localization and sparsity properties of wavelet bases allow finding a sparse solution to inverse problems by iterative minimization of a combination of the ℓ 2 norm of the data residuals and the ℓ 1 norm of the model wavelet coefficients. By validation with realistic synthetic experiments we illustrate the likely gains from our new approach in future inversions of finite-frequency seismic data.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 8
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    Flagellin Perception Varies Quantitatively in Arabidopsis thaliana and Its Relatives (2012)
    Oxford University Press
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    Publication Date: 2012-05-16
    Description: Much is known about the evolution of plant immunity components directed against specific pathogen strains: They show pervasive functional variation and have the potential to coevolve with pathogen populations. However, plants are effectively protected against most microbes by generalist immunity components that detect conserved pathogen-associated molecular patterns (PAMPs) and control the onset of PAMP-triggered immunity. In Arabidopsis thaliana , the receptor kinase flagellin sensing 2 (FLS2) confers recognition of bacterial flagellin (flg22) and activates a manifold defense response. To decipher the evolution of this system, we performed functional assays across a large set of A. thaliana genotypes and Brassicaceae relatives. We reveal extensive variation in flg22 perception, most of which results from changes in protein abundance. The observed variation correlates with both the severity of elicited defense responses and bacterial proliferation. We analyzed nucleotide variation segregating at FLS2 in A. thaliana and detected a pattern of variation suggestive of the rapid fixation of a novel adaptive allele. However, our study also shows that evolution at the receptor locus alone does not explain the evolution of flagellin perception; instead, components common to pathways downstream of PAMP perception likely contribute to the observed quantitative variation. Within and among close relatives, PAMP perception evolves quantitatively, which contrasts with the changes in recognition typically associated with the evolution of R genes.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    GATA4 Is a Critical Regulator of Gonadectomy-Induced Adrenocortical Tumorigenesis in Mice (2012)
    Oxford University Press
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    Publication Date: 2012-06-12
    Description: In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4 +/– B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2 -cre-mediated deletion of floxed Gata4 ( Gata4 F ) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4 F dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.
    Print ISSN: 0013-7227
    Topics: Medicine
    Published by Oxford University Press on behalf of The Endocrine Society.
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  • 10
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    Staging for distant metastases in operable breast cancer: a suggested expansion of the ESMO guideline recommendation for staging imaging of node-negative, hormonal receptor-negative disease (2013)
    Oxford University Press
    Details
    Publication Date: 2013-01-23
    Description: We evaluated the impact of staging procedures to detect asymptomatic distant metastases (DM) in the management of women with operable invasive breast cancer (BC, entire cohort: n = 866). Out of 472 patients with lymph node (LN)-negative disease (pN0), DM were found in four cases (detection rate: 0.8%). All four patients presented with established risk factors: hormone receptor (HR)-negative status, HER2-positive status, n = 3; ‘triple-negative’ disease, n = 1. Considering the subgroup of LN-negative patients whose tumors showed the risk factor ‘negative HR status’ ( n = 66), the detection rate of DM was 6%. The detection rates of DM in higher pN categories were as follows: pN1:1.7%; pN2:9.5%; pN3:13.5%. We generally support the international guidelines, including those published by the European Society for Medical Oncology (ESMO) which emphasize that patients with early-stage BC do not profit from radiological staging for the detection of DM and recommend refraining from this. However, we would expand these guidelines and propose that screening should be carried out in node-negative patients whose tumors show established tumor-related risk factors (e.g. HR-negative and HER2-positive status), since in this particular subcohort, the detection rate of DM is with 6% similarly high as that of patients with four to nine positive LNs.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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