1,429 research outputs found

    Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS deficient mice.

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    cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction of FSHβ and GnRH receptor genes. Herein, we analyzed reproductive function in the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is necessary for gonadotropin subunit expression, while TSHβ is unaffected. Additionally, cFOS null animals have the same sex-steroid levels, although gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls, particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA levels. Collectively, our novel findings suggest that cFOS plays a cell-specific role at multiple levels of the hypothalamic-pituitary-gonadal axis, affecting gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not GnRH neurons in the hypothalamus, thereby contributing to the overall control of reproduction

    Monoclonal antibodies against human astrocytomas and their reactivity pattern

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    The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 × 106 chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner

    Examination of acid-base properties and structural parameters of thiobarbituric acid

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    The stepwise proton-ligand stability constant of thiobarbituric acid anion was determined in an aqueous solution via pH-potentiometry at ionic strength I=0,1 and temperature T=20°C. Based on the absorption spectra analysis of thiobarbituric acid (H[2]L, H[2]thioBar) solutions in the UV-region at different pH values, it was shown that H[2]thioBar could exist in di-, mono-, and deprotonated forms. This latter fact is reflected in the particle yield H[2]L diagrams as a function of the aqueous solution pH. Besides, some geometric and physico-chemical characteristics of H2thioBar were described by means of quantum chemical calculations

    Innovating Advanced Radiation Instruments

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    STREAM is a 4-year multi-site training network that aims at career development of Early Stage Researchers (ESRs) on scientific design, construction manufacturing and of advanced radiation instrumentation. STREAM targets the development of innovative radiation-hard, smart CMOS sensor technologies for scientific and industrial applications. The platform technology developed within the project will be tested in the demanding conditions posed by the CERN LHC detectors' environment as well as European industry leaders in the field of CMOS imaging, electron microscopy and radiation sensors. This leveraging factor will allow to fine-tune the technology to meet the requirements of industrial application cases on demand such as electron microscopy and medical X-ray imaging, as well as pathway towards novel application fields such as satellite environments, industrial X-ray systems and near-infrared imaging. The project will train a new generation of creative, entrepreneurial and innovative early-stage researchers and widen their academic career and employment opportunities. The STREAM consortium is composed of 10 research organisations and 5 industrial partners; the network will provide training to 17 ESRs. STREAM structures the research and training in four scientific work-packages which span the whole value-chain from research to application: CMOS Technologies Assessment, Smart Sensor Design and Layout, Validation and Qualification, Technology Integration, and Valorization

    Robotic Technologies for Surveying Habitats and Seeking Evidence of Life: Results from the 2004 Field Experiments of the "Life in the Atacama" Project

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    The Chilean Atacama Desert is the most arid region on Earth and in several ways analogous to Mars. Evidence suggests that the interior of the Atacama is lifeless, yet where the desert meets the Pacific coastal range dessication-tolerant microorganisms are known to exist. The gradient of biodiversity and habitats in the Atacama's subregions remain unexplored and are the focus of the Life in the Atacama project. Our field investigation attempts to bring further scientific understanding of the Atacama as a habitat for life through the creation of robotic astrobiology. This involves capabilities for autonomously traversing hundreds of kilometers while deploying sensors to survey the varying geologic and biologic properties of the environment, Fig. 1. Our goal is to make genuine discoveries about the limits of life on Earth and to generate knowledge about life in extreme environments that can be applied to future planetary missions. Through these experiments we also hope to develop and practice the methods by which a rover might best be employed to survey desert terrain in search of the habitats in which life can survive, or may have in the past

    Dynamical modeling of the network controlling meiotic divisions

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    Mitosis and meiosis are both controlled by oscillations in the activities of cyclin- dependent kinase 1 (Cdk1) and the anaphase-promoting complex/cyclosome (APC/C). Nevertheless, these types of cell division differ in fundamental aspects. In mitosis, Cdk1 and APC/C-Cdc20 form a cyclical system whereby each cycle recreates the starting conditions for the next one. As a result, chromosomes duplication during S-phase alternates with chromosome segregation during M-phase. By contrast, meiosis is a linear pathway of precisely two waves of Cdk1 and APC/C-Cdc20 activity that govern the progression through one S-phase followed by two M-phases and a differentiation program dedicated to the formation of gametes or spores. Despite recent advances in our understanding of meiosis, it is unclear how the mitotic cell cycle engine is modified to regulate the two meiotic divisions. Therefore, we combined mathematical modeling with experimental studies on budding yeast to describe the general mechanism of progression through meiotic divisions with special emphasis on the regulation of the exit from meiosis II. We showed that progression through meiotic divisions is driven by a well conserved Cdk1-APC/C-Cdc20 oscillator complemented by a set of meiotic regulators in order to perform two, and only two, meiotic divisions. The machinery that terminates the oscillations after completion of meiosis II consists of a meiosis I-specific mechanism that unleashes the irreversible inactivation of M-phase regulators after the second wave of APC/C-Cdc20 activity, thereby preventing cells from undergoing an additional third division. Here, we describe the roles of the two main APC/C co- activators, Ama1 and Cdc20, in triggering the exit from meiosis and in terminating the oscillations. We show that Ama1 acts as a terminator of the meiotic oscillations, while Cdc20 is important for the proper timing of the exit from meiosis II. We propose that in the absence of Ama1, the properties of the system change, allowing Cdc20 to adopt the function of the terminator precisely after meiosis II. In addition, we evaluate an APC/C-independent mechanisms, which might be important for preventing a third meiotic division
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