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  • 1
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    Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia (2014)
    Springer Nature
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    Publication Date: 2014-12-17
    Description: Article Loss of olfactory function is one of the many symptoms of the ciliopathy Bardet–Biedl syndrome. Williams et al . show that Bardet–Biedl proteins are components of intraflagellar transport particles within cilia, and directly visualize their trafficking in native mammalian olfactory neurons. Nature Communications doi: 10.1038/ncomms6813 Authors: Corey L. Williams, Jeremy C. McIntyre, Stephen R. Norris, Paul M. Jenkins, Lian Zhang, Qinglin Pei, Kristen Verhey, Jeffrey R. Martens
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 2
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    Redox Mediator Effect on Water Oxidation in a Ruthenium-Based Chromophore–Catalyst Assembly (2013)
    American Chemical Society (ACS)
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    Publication Date: 2013-02-02
    Description: Journal of the American Chemical Society DOI: 10.1021/ja311645d
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 3
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    RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma [Medical Sciences] (2011)
    National Academy of Sciences
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    Publication Date: 2011-02-23
    Description: Neuroblastoma is a childhood cancer that is often fatal despite intense multimodality therapy. In an effort to identify therapeutic targets for this disease, we performed a comprehensive loss-of-function screen of the protein kinome. Thirty kinases showed significant cellular cytotoxicity when depleted, with loss of the cell cycle checkpoint kinase 1 (CHK1/CHEK1) being the most potent. CHK1 mRNA expression was higher in MYC–Neuroblastoma-related (MYCN)–amplified (P 〈 0.0001) and high-risk (P = 0.03) tumors. Western blotting revealed that CHK1 was constitutively phosphorylated at the ataxia telangiectasia response kinase target site Ser345 and the autophosphorylation site Ser296 in neuroblastoma cell lines. This pattern was also seen in six of eight high-risk primary tumors but not in control nonneuroblastoma cell lines or in seven of eight low-risk primary tumors. Neuroblastoma cells were sensitive to the two CHK1 inhibitors SB21807 and TCS2312, with median IC50 values of 564 nM and 548 nM, respectively. In contrast, the control lines had high micromolar IC50 values, indicating a strong correlation between CHK1 phosphorylation and CHK1 inhibitor sensitivity (P = 0.0004). Furthermore, cell cycle analysis revealed that CHK1 inhibition in neuroblastoma cells caused apoptosis during S-phase, consistent with its role in replication fork progression. CHK1 inhibitor sensitivity correlated with total MYC(N) protein levels, and inducing MYCN in retinal pigmented epithelial cells resulted in CHK1 phosphorylation, which caused growth inhibition when inhibited. These data show the power of a functional RNAi screen to identify tractable therapeutical targets in neuroblastoma and support CHK1 inhibition strategies in this disease.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Influence of anthropogenic aerosols and the Pacific Decadal Oscillation on tropical belt width (2014)
    Springer Nature
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    Publication Date: 2014-03-29
    Description: Nature Geoscience 7, 270 (2014). doi:10.1038/ngeo2091 Authors: Robert J. Allen, Joel R. Norris & Mahesh Kovilakam The tropical belt has widened by several degrees latitude since 1979, as evidenced by shifts in atmospheric circulation and climate zones. Global climate models also simulate tropical belt widening, but less so than observed. Reasons for this discrepancy and the mechanisms driving the expansion are uncertain. Here we analyse multidecadal variability in tropical belt width since 1950 using the Coupled Model Intercomparison Project Phase 5 climate model runs and find that simulated rates of tropical expansion over the past 30 years—particularly in the Northern Hemisphere—are in better agreement with observations than previous models. We find that models driven by observed sea surface temperatures over this interval yield the largest rate of tropical expansion. We link the tropical expansion in the Northern Hemisphere to the leading pattern of sea surface temperature variability in the North Pacific, the Pacific Decadal Oscillation. We also find, both from models and observations, that the tropical belt contracted in the Northern Hemisphere from 1950 to 1979, coincident with the reversal of the Pacific Decadal Oscillation trend. In both time periods, anthropogenic aerosols act to modify the Pacific Decadal Oscillation and therefore contribute to the width of the tropical belt. We conclude that tropical expansion and contraction are influenced by multidecadal sea surface temperature variability associated with both the Pacific Decadal Oscillation and anthropogenic aerosols.
    Print ISSN: 1752-0894
    Electronic ISSN: 1752-0908
    Topics: Geosciences
    Published by Springer Nature
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  • 5
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    Photoinduced Electron Transfer in a Chromophore–Catalyst Assembly Anchored to TiO2 (2012)
    American Chemical Society (ACS)
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    Publication Date: 2012-11-10
    Description: Journal of the American Chemical Society DOI: 10.1021/ja3084362
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 6
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    Recent Northern Hemisphere tropical expansion primarily driven by black carbon and tropospheric ozone (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-05-19
    Description: Observational analyses have shown the width of the tropical belt increasing in recent decades as the world has warmed. This expansion is important because it is associated with shifts in large-scale atmospheric circulation and major climate zones. Although recent studies have attributed tropical expansion in the Southern Hemisphere to ozone depletion, the drivers of Northern Hemisphere expansion are not well known and the expansion has not so far been reproduced by climate models. Here we use a climate model with detailed aerosol physics to show that increases in heterogeneous warming agents--including black carbon aerosols and tropospheric ozone--are noticeably better than greenhouse gases at driving expansion, and can account for the observed summertime maximum in tropical expansion. Mechanistically, atmospheric heating from black carbon and tropospheric ozone has occurred at the mid-latitudes, generating a poleward shift of the tropospheric jet, thereby relocating the main division between tropical and temperate air masses. Although we still underestimate tropical expansion, the true aerosol forcing is poorly known and could also be underestimated. Thus, although the insensitivity of models needs further investigation, black carbon and tropospheric ozone, both of which are strongly influenced by human activities, are the most likely causes of observed Northern Hemisphere tropical expansion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, Robert J -- Sherwood, Steven C -- Norris, Joel R -- Zender, Charles S -- England -- Nature. 2012 May 16;485(7398):350-4. doi: 10.1038/nature11097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Sciences, University of California, Riverside 92521, USA. rjallen@ucr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22596159" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols/analysis/chemistry ; Atmosphere/*chemistry ; Gases/analysis ; Geography ; Greenhouse Effect/*statistics & numerical data ; *Hot Temperature ; Human Activities ; Models, Theoretical ; Ozone/*analysis ; Seasons ; Soot/*analysis ; *Tropical Climate
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    A close halo of large transparent grains around extreme red giant stars (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-04-14
    Description: An intermediate-mass star ends its life by ejecting the bulk of its envelope in a slow, dense wind. Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust, which is then accelerated by radiation pressure, entraining the gas and driving the wind. Explaining the amount of mass loss, however, has been a problem because of the difficulty of observing tenuous gas and dust only tens of milliarcseconds from the star. For this reason, there is no consensus on the way sufficient momentum is transferred from the light from the star to the outflow. Here we report spatially resolved, multiwavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the Hertzsprung-Russell diagram. When imaged in scattered light, dust shells were found at remarkably small radii (less than about two stellar radii) and with unexpectedly large grains (about 300 nanometres in radius). This proximity to the photosphere argues for dust species that are transparent to the light from the star and, therefore, resistant to sublimation by the intense radiation field. Although transparency usually implies insufficient radiative pressure to drive a wind, the radiation field can accelerate these large grains through photon scattering rather than absorption--a plausible mass loss mechanism for lower-amplitude pulsating stars.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norris, Barnaby R M -- Tuthill, Peter G -- Ireland, Michael J -- Lacour, Sylvestre -- Zijlstra, Albert A -- Lykou, Foteini -- Evans, Thomas M -- Stewart, Paul -- Bedding, Timothy R -- England -- Nature. 2012 Apr 11;484(7393):220-2. doi: 10.1038/nature10935.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sydney Institute for Astronomy, School of Physics, University of Sydney, New South Wales 2006, Australia. bnorris@physics.usyd.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498626" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 8
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    Representation of the biosphere in post-closure assessments for the UK geological disposal programme (2013)
    Mineralogical Society of Great Britain and Ireland
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    Publication Date: 2013-01-30
    Description: This paper gives an overview of the Nuclear Decommissioning Authority, Radioactive Waste Management Directorate approach to representing the biosphere in post-closure safety assessment studies. The assessments consider potential releases of radionuclides and chemically toxic substances from a geological disposal facility that may reach the biosphere by transport in groundwater and gas. It gives an outline of the key processes and understanding underpinning the representation of the biosphere and how the biosphere may evolve over the long timescales of relevance to post-closure safety. The current biosphere assessment approach and associated models are supported by research studies and collaboration that ensure they are consistent with international recommendations. Research studies are also commissioned to reduce uncertainty surrounding key contaminants and potential exposure pathways and to help ensure that the approach and models are adaptable and flexible enough to incorporate future developments, as the geological disposal programme moves towards site selection.
    Print ISSN: 0026-461X
    Electronic ISSN: 1471-8022
    Topics: Geosciences
    Published by Mineralogical Society of Great Britain and Ireland
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  • 9
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    On global changes in effective cloud height (2012)
    Wiley
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    Publication Date: 2012-10-06
    Description: Measurements by the Multiangle Imaging SpectroRadiometer (MISR) instrument exhibit a decreasing trend in global mean effective cloud top height (2000–2011). Here we show that this trend is likely related to an artifact in the data present during the early years of the MISR mission that caused a systematic reduction in the number of retrievals of clouds at lower elevations relative to clouds at higher elevations. After the application of a post-hoc method for removing the bias associated with missing retrievals the MISR effective cloud height anomalies exhibit a positive trend over time.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 10
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    Evaluation of multidecadal variability in CMIP5 surface solar radiation and inferred underestimation of aerosol direct effects over Europe, China, Japan and India (2013)
    Wiley
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    Publication Date: 2013-04-23
    Description: [1]  Observations from the Global Energy Balance Archive indicate regional decreases in all sky surface solar radiation from ~1950s-1980s, followed by an increase during the 1990s. These periods are popularly called dimming and brightening, respectively.Removal of the radiative effects of cloud cover variability from all sky surface solar radiation results in a quantity called “clear sky proxy” radiation, in which multidecadal trends can be seen more distinctly, suggesting aerosol radiative forcing as a likely cause. Prior work has shown climate models from the Coupled Model Intercomparison Project 3 (CMIP3) generally underestimate the magnitude of these trends, particularly over China and India. Here, we perform a similar analysis with 173 simulations from 42 climate models participating in the new CMIP5. Results show negligible improvement over CMIP3, as CMIP5 dimming trends over four regions–Europe, China, India and Japan–are all underestimated. This bias is largest for both India and China, where the multi-model mean yields a decrease in clear sky proxy radiation of −1.3 ± 0.3 and −1.2 ± 0.2 W m −2 decade −1 , respectively, compared to observed decreases of −6.5 ± 0.9 and −8.2 ± 1.3 W m −2 decade −1 . Similar underestimation of the observed dimming over Japan exists, with the CMIP5 mean dimming ~20% as large as observed. Moreover, not a single simulation reproduces the magnitude of the observed dimming trend for these three regions. Relative to dimming, CMIP5 models better simulate the observed brightening, but significant underestimation exists for both China and Japan. Overall, no individual model performs particularly well for all four regions. Model biases do not appear to be related to the use of prescribed versus prognostic aerosols, or to aerosol indirect effects. However, models exhibit significant correlations between clear sky proxy radiation and several aerosol-related fields, most notably aerosol optical depth (AOD), and absorption AOD. This suggests model underestimation of the observed trends is related to underestimation of aerosol direct radiative forcing and/or deficient aerosol emission inventories.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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