Mediation of photosynthetic redox signals in the regulation of plant gene expression

The presented work contributes novel aspects to the understanding of function and co-action of cellular signalling networks in higher plants in the course of acclimation to a changing light environment. The results show that redox signals generated in the photosynthetic electron transport chain have a deeper impact on the cellular signalling network as supposed so far. It was proven that the photosynthetic apparatus acts as an important sensor for changes in the light environment of land plants and that signals originating from the redox state of electron transport components are an own class of plastid signals targeted to the nucleus. From the obtained data, a model is proposed which shows a possible signal transduction derived from the photosynthetic electron transport targeting nuclear gene expression independently of cytosolic photoreceptors. Furthermore a regulatory mechanism for chloroplast gene expression via a phosphorylation cascade starting with the kinase responsible for LHCII phosphorylation is suggested

Radio astrometry with chromatic AGN core positions

Aims: The effect of frequency-dependent AGN core positions (``core-shifts'') on radio Very Long Baseline Interferometry (VLBI) global astrometry measurements is investigated. Methods: The basic equations relating to VLBI astrometry are reviewed, including the effects of source structure. A power-law representation of core-shifts, based on both observations and theoretical considerations of jet conditions, is incorporated. Results: It is shown that, in the presence of core-shifts, phase and group-delay astrometry measurements yield different positions. For a core displacement from the jet base parametrized by Delta x (lambda) = k lambda^beta group delays measure a ``reduced'' core-shift of (1-beta) Delta x (lambda). For the astrophysically-significant case of beta = 1, group delays measure no shift at all, giving the position of the jet base. At 8.4 GHz an estimated typical offset between phase and group-delay positions of ~170 uas is smaller than the current ~250 uas precision of group-delay positions of the sources used to define the ICRF; however, this effect must be taken into account for future measurements planned with improved accuracy when comparing with optical positions of AGN to be obtained with the GAIA mission.Comment: Accepted for publication in Astronomy & Astrophysics, 4 page

High-throughput cell-based compound screen identifies pinosylvin methyl ether and tanshinone IIA as inhibitors of castration-resistant prostate cancer

Current treatment options for castration-resistant prostate cancer (CRPC) are limited. In this study, a high-throughput screen of 4910 drugs and drug-like molecules was performed to identify antiproliferative compounds in androgen ablated prostate cancer cells. The effect of compounds on cell viability was compared in androgen ablated LNCaP prostate cancer cells and in LNCaP cells grown in presence of androgens as well as in two non-malignant prostate epithelial cells (RWPE-1 and EP156T). Validation experiments of cancer specific anti-proliferative compounds indicated pinosylvin methyl ether (PSME) and tanshinone IIA as potent inhibitors of androgen ablated LNCaP cell proliferation. PSME is a stilbene compound with no previously described antineoplastic activity whereas tanshinone IIA is currently used in cardiovascular disorders and proposed as a cancer drug. To gain insights into growth inhibitory mechanisms in CRPC, genome-wide gene expression analysis was performed in PSME- and tanshinone IIA-exposed cells. Both compounds altered the expression of genes involved in cell cycle and steroid and cholesterol biosynthesis in androgen ablated LNCaP cells. Decrease in androgen signalling was confirmed by reduced expression of androgen receptor and prostate specific antigen in PSME- or tanshinone IIA-exposed cells. Taken together, this systematic screen identified a novel anti-proliferative agent, PSME, for CRPC. Moreover, our screen confirmed tanshinone IIA as well as several other compounds as potential prostate cancer growth inhibitors also in androgen ablated prostate cancer cells. These results provide valuable starting points for preclinical and clinical studies for CRPC treatment

Absolute kinematics of radio source components in the complete S5 polar cap sample. III. First wide-field high-precision astrometry at 15.4 GHz

We report on the first wide-field, high-precision astrometric analysis of the 13 extragalactic radio sources of the complete S5 polar cap sample at 15.4 GHz. We describe new algorithms developed to enable the use of differenced phase delays in wide-field astrometric observations and discuss the impact of using differenced phase delays on the precision of the wide-field astrometric analysis. From this global fit, we obtained estimates of the relative source positions with precisions ranging from 14 to 200 $\mu$as at 15.4 GHz, depending on the angular separation of the sources (from $\sim$1.6 to $\sim$20.8 degrees). These precisions are $\sim$10 times higher than the achievable precisions using the phase-reference mapping technique.Comment: 9 pages, 7 figure

Absolute kinematics of radio source components in the complete S5 polar cap sample. IV. Proper motions of the radio cores over a decade and spectral properties

We have carried out a high-precision astrometric analysis of two very-long-baseline-interferometry (VLBI) epochs of observation of the 13 extragalactic radio sources in the complete S5 polar cap sample. The VLBI epochs span a time baseline of 10 years and enable us to achieve precisions in the proper motions of the source cores up to a few micro-arcseconds per year. The observations were performed at 14.4 GHz and 43.1 GHz, and enable us to estimate the frequency core-shifts in a subset of sources, for which the spectral-index distributions can be computed. We study the source-position stability by analysing the changes in the relative positions of fiducial source points (the jet cores) over a decade. We find motions of 0.1-0.9 mas among close-by sources between the two epochs, which imply drifts in the jet cores of approximately a few tens of micro-as per year. These results have implications for the standard Active Galactic Nucleus (AGN) jet model (where the core locations are supposed to be stable in time). For one of our sources, 0615+820, the morphological and spectral properties in year 2010, as well as the relative astrometry between years 2000 and 2010, suggest the possibility of either a strong parsec-scale interaction of the AGN jet with the ISM, a gravitational lens with ~1 mas diameter, or a resolved massive binary black hole

BioCPR–A Tool for Correlation Plots

A gene is a sequence of DNA bases through which genetic information is passed on to the next generation. Most genes encode for proteins that ultimately control cellular function. Understanding the interrelation between genes without the application of statistical methods can be a daunting task. Correlation analysis is a powerful approach to determine the strength of association between two variables (e.g., gene-wise expression). Moreover, it becomes essential to visualize this data to establish patterns and derive insight. The most common method for gene expression visualization is to use correlation heatmaps in which the colors of the plot represent strength of co-expression. In order to address this requirement, we developed a visualization tool called BioCPR: Biological Correlation Plots in R. This tool performs both correlation analysis and subsequent visualization in the form of an interactive heatmap, improving both usability and interpretation of the data. BioCPR is an R Shiny-based application and can be run locally in Rstudio or a web browser.</p

Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy

Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein-and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age + HRT-related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17 beta-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17 beta-estradiol, fat-, glucose-and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature.Peer reviewe

Identification of MicroRNAs Inhibiting TGF-beta-Induced IL-11 Production in Bone Metastatic Breast Cancer Cells

Peer reviewe

A relational database to identify differentially expressed genes in the endometrium and endometriosis lesions

Endometriosis is a common inflammatory estrogen-dependent gynecological disorder, associated with pelvic pain and reduced fertility in women. Several aspects of this disorder and its cellular and molecular etiology remain unresolved. We have analyzed the global gene expression patterns in the endometrium, peritoneum and in endometriosis lesions of endometriosis patients and in the endometrium and peritoneum of healthy women. In this report, we present the EndometDB, an interactive web-based user interface for browsing the gene expression database of collected samples without the need for computational skills. The EndometDB incorporates the expression data from 115 patients and 53 controls, with over 24000 genes and clinical features, such as their age, disease stages, hormonal medication, menstrual cycle phase, and the different endometriosis lesion types. Using the web-tool, the end-user can easily generate various plot outputs and projections, including boxplots, and heatmaps and the generated outputs can be downloaded in pdf-format.Peer reviewe

High-Throughput Transcriptomic and RNAi Analysis Identifies AIM1, ERGIC1, TMED3 and TPX2 as Potential Drug Targets in Prostate Cancer

Peer reviewe