204 research outputs found

    FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

    Get PDF
    Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

    Cosmic rays and molecular clouds

    Full text link
    This paper deals with the cosmic-ray penetration into molecular clouds and with the related gamma--ray emission. High energy cosmic rays interact with the dense gas and produce neutral pions which in turn decay into two gamma rays. This makes molecular clouds potential sources of gamma rays, especially if they are located in the vicinity of a powerful accelerator that injects cosmic rays in the interstellar medium. The amplitude and duration in time of the cosmic--ray overdensity around a given source depend on how quickly cosmic rays diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray observations of molecular clouds can be used both to locate the sources of cosmic rays and to constrain the properties of cosmic-ray diffusion in the Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics 2012, 27 pages, 10 figure

    E-Business, The Impact of The Regional Government Development (APBD) on Information and Communication Development in Indonesia

    Get PDF
    The decline of development delived from natural resources in several regions in Indonesia requires local governments to make a breakthrough in increasing revenues beyond natural resources, including through increased revenue in the field of information technology. The purpose of this study is to analyze the impact of the regional government development (APBD) on information and communication development in Indonesia. By using correlational research, it is known that all of APBD sub variables have a high correlation in increasing Gross Regional Domestic Product (GRDP) of Information and Communication in Indonesia, only sub-variable of surplus/deficit development, unexpected development sub-variable, sub-variable of development aid to province/regency/city and village government, and sub-variable of development special allocations that have not a significant correlation to increase of GRDP of Information and Communication in Indonesia. There is 86,7% of APBD variable influence the increase of GRDP of Information and Communication, while the increase of 15,3% of Information and Communication GRDP influenced by other factors aside from APBD. It shows the strong impact of APBD on increasing GRDP of Information and Communication

    E-Business, Airport Development and Its Impact on the Increasing of Information of Communication Development in Indonesia

    Get PDF
    The increasing number of the internet usage by households have an effect on the tourism sector. On the other hand, the aviation industry is growing as one of the development centers. This study aims to analyze the impact of information and communication development to airport performance in Indonesia. This is a correlation research with 151 of airports in Indonesia as a population. The sampling technique was done by using total sampling. The results of correlation (R) indicates the Gross Regional Domestic Product (GRDP) of Information and Communication has a relatively strong relationship with the Airport Performance. Meanwhile the results of Adjusted R test shows that they are other factors in increasing GRDP of Information and Communication besides Airport Performance. It shows the low impact of Information and Communication GRDP to the Airport Performance

    The Correlations Between Airport Suistainability and Indonesian Economic Growth

    Get PDF
    This study aims to analyze the correlation between airport performance with Gross domestic product-regional (GDP-regional) performance. This research uses quantitative research method with correlation study approach. Based on the T-Value Test Result, the T-value for the Airport Performance variable is 14,264. T-Value Test Result and compared with T-table equal to 1,976 (significant level 0,05) hence T-Count> T-Table so variable of Airport Perform predicted have significant correlation to GDP-regional. This means that good airport performance will either improve the performance of Water Supply, Sewerage, Waste Management and Remediation Activities; Wholesale and Retail Trade; Repair of Motor Vehicles and Motorcycles; Accomodation and Food Service Activities; Financial and Isurance Activities; Business Activities; Public Administration and Defence; Compulsory Social Security; Education; human Health and Social Work Activities; Other Services Activities; Manufacturing; and Electricity and Gas, better

    Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin

    Get PDF
    We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73±0.09 µm vs 1.91±0.08 µm, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo
    • …
    corecore