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Search Results: 1 - 10 of 297378 matches for " Jürgen Dittmer "
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The Biology of the Ets1 Proto-Oncogene
Jürgen Dittmer
Molecular Cancer , 2003, DOI: 10.1186/1476-4598-2-29
Abstract: Ets proteins comprise a family of transcription factors that share a unique DNA binding domain, the Ets domain [1-4]. The name "Ets" stems from a sequence that was detected in an avian erythroblastosis virus, E26, where it formed a transforming gene together with Δgag and c-myb [5,6]. The newly discovered sequence was called E26 transformation specific sequence or Ets. Later, a cellular homologue to the viral ets (v-ets) gene, c-ets1, was found suggesting that v-ets derived from c-ets1 [7,8].The c-Ets1 protein is closely related to c-Ets2. It is believed that these two proteins derived from the same ancestor gene by duplication [9,10]. The genomes of Drosophila and sea urchin contain only one Ets1-related gene, D-ets2 (Pointed) and SU-ets2, respectively, whereas birds, reptiles, amphibians and mammals harbor both the ets1 and ets2 genes [11,12]. In humans, the ets1 and ets2 genes are located on two distinct chromosomes, ets1 on chromosome #11, ets2 on chromosome #21 [7]. No ets1-related gene has been found in the genome of the Caenorhabditis elegans, although this nematode worm does express a variety of other Ets proteins [13].In birds and reptiles, the c-ets1 locus contains two different start sites leading to the expression of p68c-ets1 and p54c-ets1. These two proteins differ in their N-terminal sequence [14]. Exons α (I) and β (II) code for the N-terminus of p68c-ets1, whereas exon I54 (A) encodes the N-terminus of p54c-ets1 (Fig. 1). The exon β domain of p68c-ets1 shows a high degree of homology to the N-terminus of c-Ets2 and was thus called the Ets1-beta/Ets2-conserved sequence (BEC). In mammals, only exon I54 is present, therefore, p68c-ets1 is not expressed.The human TATA-less ets1 gene contains eight exons (A, III-IX) [15]. Transcripts either harbor all exons or lack exon IV- or exon VII- or exon IV/VII-specific sequence [16]. Only two proteins are generated from these RNAs, p54c-ets1 (full length Ets1) and p42c-ets1 (ΔVII-Ets1) (Fig. 1). The Ets1 protein
Mesenchymal Stem Cells: “Repair Cells” that Serve Wounds and Cancer?
Jürgen Dittmer
The Scientific World Journal , 2010, DOI: 10.1100/tsw.2010.119
Abstract:
Cyclic AMP Enhances TGFβ Responses of Breast Cancer Cells by Upregulating TGFβ Receptor I Expression
Ilka Oerlecke, Elke Bauer, Angela Dittmer, Benjamin Leyh, Jürgen Dittmer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054261
Abstract: Cellular functions are regulated by complex networks of many different signaling pathways. The TGFβ and cAMP pathways are of particular importance in tumor progression. We analyzed the cross-talk between these pathways in breast cancer cells in 2D and 3D cultures. We found that cAMP potentiated TGFβ-dependent gene expression by enhancing Smad3 phosphorylation. Higher levels of total Smad3, as observed in 3D-cultured cells, blocked this effect. Two Smad3 regulating proteins, YAP (Yes-associated protein) and TβRI (TGFβ receptor 1), were responsive to cAMP. While YAP had little effect on TGFβ-dependent expression and Smad3 phosphorylation, a constitutively active form of TβRI mimicked the cAMP effect on TGFβ signaling. In 3D-cultured cells, which show much higher levels of TβRI and cAMP, TβRI was unresponsive to cAMP. Upregulation of TβRI expression by cAMP was dependent on transcription. A proximal TβRI promoter fragment was moderately, but significantly activated by cAMP suggesting that cAMP increases TβRI expression at least partially by activating TβRI transcription. Neither the cAMP-responsive element binding protein (CREB) nor the TβRI-regulating transcription factor Six1 was required for the cAMP effect. An inhibitor of histone deacetylases alone or together with cAMP increased TβRI expression by a similar extent as cAMP alone suggesting that cAMP may exert its effect by interfering with histone acetylation. Along with an additive stimulatory effect of cAMP and TGFβ on p21 expression an additive inhibitory effect of these agents on proliferation was observed. Finally, we show that mesenchymal stem cells that interact with breast cancer cells can simultaneously activate the cAMP and TGFβ pathways. In summary, these data suggest that combined effects of cAMP and TGFβ, as e.g. induced by mesenchymal stem cells, involve the upregulation of TβRI expression on the transcriptional level, likely due to changes in histone acetylation. As a consequence, cancer cell functions such as proliferation are affected.
Interfering with TGFβ-induced Smad3 nuclear accumulation differentially affects TGFβ-dependent gene expression
Ralph K Lindemann, Alfred Nordheim, Jürgen Dittmer
Molecular Cancer , 2003, DOI: 10.1186/1476-4598-2-20
Abstract: Our results show that these inhibitors delay the onset of TGFβ-induced nuclear accumulation of Smad3 and reduces its amplitude. This effect was accompanied by a strong reduction in TGFβ-responsivess of the slow-responder genes pthrp, pai-1 and upa, while the reactivity of the fast-responder gene smad7 to TGFβ remained almost unchanged. Neither was the TGFβ response of the fast-responder ese-1/esx gene, whose expression we found to be strongly downregulated by TGFβ, affected by the inhibitors.The data show that SB-202190 and SB-203580 suppress TGFβ-dependent activation of genes that are important for the acquisition of invasive behavior, while having no effect on the expression of the natural TGFβ inhibitor Smad7. This suggests that these compounds are potent inhibitors of malignant behavior of cancer cells.Malignant tumor cells frequently show deregulation and hyperactivation of signalling pathways, one of which is represented by the TGFβ signal transduction pathway [1]. TGFβ has been shown to potently inhibit proliferation of most epithelial, endothelial and hematopoietic cells [2]. However, during tumor progression malignant cells may become refractory to TGFβ-mediated cell cycle arrest. In later stages of tumorigenesis, TGFβ can act as a stimulator of invasion and metastasis [3] acting directly on the tumor cells or inducing angiogenesis and facilitating local and systemic immunosuppression, respectively [4]. For example, TGFβ may stimulate the expression of proteases such as uPA, MMP-3 or MMP-9, enzymes frequently overexpressed in invasive tumor cells [5,6].TGFβ signals through a heteromeric receptor complex of type II and type I receptor serine-threonine kinases, which activates the downstream Smad signal transduction pathway [7]. After TGFβ binding to the receptor complex, the TGFβ type II receptor kinase phosphorylates TGFβ type I receptor which inititates the downstream response by phosphorylating receptor-regulated Smads (R-Smads), such as Smad2 and Smad3.
A torsional sensor for MEMS-based RMS voltage measurements
J. Dittmer,R. Judaschke,S. Büttgenbach
Advances in Radio Science : Kleinheubacher Berichte , 2008,
Abstract: RF voltage measurement based on electrostatic RMS voltage-to-force conversion is an alternative method in comparison to the conventional thermal power dissipation method. It is based on a mechanical force induced by an RF voltage applied to a micro-mechanical system. For a theoretically adequate resolution and high precision measurements, the necessary geometrical dimensions of the sensor require the application of micro machining. In this contribution, the dependence between electrical and geometrical properties of different sensor designs is investigated. Based on these results, problems related to practical micro-machining and solutions with respect to possible sensor realizations are discussed. The evolution of different sensor generations is shown.
Operator Splitting Method for Coupled Problems:Transport and Maxwell Equations  [PDF]
Jürgen Geiser
American Journal of Computational Mathematics (AJCM) , 2011, DOI: 10.4236/ajcm.2011.13019
Abstract: In this article a new approach is considered for implementing operator splitting methods for transport problems, influenced by electric fields. Our motivation came to model PE-CVD (plasma-enhanced chemical vapor deposition) processes, means the flow of species to a gas-phase, which are influenced by an electric field. Such a field we can model by wave equations. The main contributions are to improve the standard discretization schemes of each part of the coupling equation. So we discuss an improvement with implicit Runge- Kutta methods instead of the Yee’s algorithm. Further we balance the solver method between the Maxwell and Transport equation.
Development of a computer vision system to monitor pig locomotion  [PDF]
Jrgen Kongsro
Open Journal of Animal Sciences (OJAS) , 2013, DOI: 10.4236/ojas.2013.33038
Abstract: Avoiding lameness or leg weakness in pig production is crucial to reduce cost, improve animal welfare and meat quality. Detection of lameness detection by the use of vision systems may assist the farmer or breeder to obtain a more accurate and robust measurement of lameness. The paper presents a low-cost vision system for measuring the locomotion of moving pigs based on motion detection, frame-grabbing and multivariate image analysis. The first step is to set up a video system based on web camera technology and choose a test area. Secondly, a motion detection and data storage system are used to build a processing system of video data. The video data are analyzed measuring the properties of each image, stacking them for each animal and then analyze these stacks using multivariate image analysis. The system was able to obtain and decompose information from these stacks, where components could be extracted, representing a particular motion pattern. These components could be used to classify or score animals according to this pattern, which might be an indicator of lameness. However, further improvement is needed with respect to standardization of herding, test area and tracking of animals in order to have a robust system to be used in a farm environment.
Three SRA-Domain Methylcytosine-Binding Proteins Cooperate to Maintain Global CpG Methylation and Epigenetic Silencing in Arabidopsis
Hye Ryun Woo,Travis A. Dittmer,Eric J. Richards
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000156
Abstract: Methylcytosine-binding proteins decipher the epigenetic information encoded by DNA methylation and provide a link between DNA methylation, modification of chromatin structure, and gene silencing. VARIANT IN METHYLATION 1 (VIM1) encodes an SRA (SET- and RING-associated) domain methylcytosine-binding protein in Arabidopsis thaliana, and loss of VIM1 function causes centromere DNA hypomethylation and centromeric heterochromatin decondensation in interphase. In the Arabidopsis genome, there are five VIM genes that share very high sequence similarity and encode proteins containing a PHD domain, two RING domains, and an SRA domain. To gain further insight into the function and potential redundancy among the VIM proteins, we investigated strains combining different vim mutations and transgenic vim knock-down lines that down-regulate multiple VIM family genes. The vim1 vim3 double mutant and the transgenic vim knock-down lines showed decreased DNA methylation primarily at CpG sites in genic regions, as well as repeated sequences in heterochromatic regions. In addition, transcriptional silencing was released in these plants at most heterochromatin regions examined. Interestingly, the vim1 vim3 mutant and vim knock-down lines gained ectopic CpHpH methylation in the 5S rRNA genes against a background of CpG hypomethylation. The vim1 vim2 vim3 triple mutant displayed abnormal morphological phenotypes including late flowering, which is associated with DNA hypomethylation of the 5′ region of FWA and release of FWA gene silencing. Our findings demonstrate that VIM1, VIM2, and VIM3 have overlapping functions in maintenance of global CpG methylation and epigenetic transcriptional silencing.
Treatment of chronic vulvovaginal candidiasis with posaconazole and ciclopiroxolamine  [PDF]
Hans-Jürgen Tietz
Health (Health) , 2010, DOI: 10.4236/health.2010.26077
Abstract: Therapy of chronic recurrent vulvovaginal can- didiasis (VVC) caused by Candida glabrata is still rare in comparison to C. albicans infection, but therapy remains more difficult. Combination therapy with topical antifungals may improve therapy outcome, but still standard agents as fluconazole or itraconazole often fail. Posaconazole is a new systemic triazole with a wide antifungal spectrum including rare Candida species. Up to now, no clinical trials with posa- conazole in chronic recurrent VVC have been undertaken. Here, first results of the application of a new therapy regimen consisting of oral posaconazole in combination with topical ciclopiroxolamine are presented. 15 patients with chronic recurrent VVC caused by C. glabrata have been treated. 14 of these patients experienced successful therapy, clinical and mycological cure 30 days after begin of therapy has been observed. Long-term results are promising, as in 4 patients clinical and mycologic cure persists for more than 1 year up to now.
Periodic Signals of the Milky Way Concealed in Terrestrial Sedimentary Basin Fills and in Planetary Magmatism?  [PDF]
Heinz-Jürgen Brink
International Journal of Geosciences (IJG) , 2015, DOI: 10.4236/ijg.2015.68067
Abstract: Long periodic geodynamic processes with durations between 150 and 600 Million years appear to be in phase with similar galactic cycles, caused by the path of the solar system through the spiral arms of the Milky Way. This path is assumed by some authors to cause climate change due to cosmic ray fluctuations, affecting the cloud formation and the related albedo of the Earth, which periodically lead to glaciations every 150 Ma. With the glaciations, the sea level fluctuates accordingly. Subsequently, the varying sizes of shallow seas are causing periodic changes of the Moon’stidal dissipation, which affects presumably other geodynamic processes on the Earth. The Moonmay therefore synchronize directly or indirectly long periodic Phanerozoic cycles (sea level, orogeny, magmatism, sedimentation, etc.) with the Milky Way. As sea level fluctuations, orogeny, sedimentation and magmatism can be described as members of a geodynamic feedback system; no apparent reasons appear to be required to assign a cause of the cyclicity to agents outside of thegalactic-climatically synchronized Earth-Moon system. However, recent observations of youngvolcanism on the near Earth terrestrial planets may require a new understanding. Magmatic/volcanic episodes on Venus, Mars and Mercury as well as on the Earth’s Moon are apparently contemporaneous thermal events accompanying increased magmatic/volcanic activities on theEarth,following a 300 myr cycle. Therefore, a collateral galactic thermal source within the Milky Way
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