37 research outputs found

    Comprehensive molecular characterization of the hippo signaling pathway in cancer

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    Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

    Tropospheric emissions: Monitoring of pollution (TEMPO)

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    TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1kmN/S x 4.4 kmE/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial foot print resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host space craft to provide a modest cost mission that measures the spectra required to retrieve ozone(O3), nitrogen dioxide(NO2), sulfur dioxide(SO2), formaldehyde(H2CO), glyoxal (C2H2O2), bromine monoxide(BrO), IO (iodine monoxide), water vapor, aerosols, cloud parameters, ultraviolet radiation,and foliage properties. TEMPO thus measures the major elements,directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lower most troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real- time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments

    A guide to in vivo optogenetic applications for cerebellar studies

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    The mammalian cerebellum consists of a superficial cortex and centrally located output nuclei, which together with brainstem nuclei are organized in a modular fashion. Regardless of the function, these cerebellar modules consist of the same cell types, and their connectivity has been unraveled to some detail using electrical stimulation experiments. To unravel the highest level of detail, cell-specific stimulation experiments are warranted, which cannot be accomplished using electrical stimulation. To reach this unprecedented level of specificity, optogenetic applications are now being implemented in cerebellar studies. Due to the extensive knowledge about cell-specific markers in both the cerebellar cortex and the cerebellar nuclei, optogenetics can be applied cell specifically. Ideally the anatomical and electrophysiological characteristics of the cerebellum can be utilized for designing future optogenetic studies. In this chapter we review the opportunities and pitfalls for optogenetic studies in the cerebellum. We provide insights into the technical issues at hand and which solutions are currently available
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