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  • 1
    Publication Date: 2010-07-20
    Description: Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML, can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takahiro -- Kwon, Hyog Young -- Zimdahl, Bryan -- Congdon, Kendra L -- Blum, Jordan -- Lento, William E -- Zhao, Chen -- Lagoo, Anand -- Gerrard, Gareth -- Foroni, Letizia -- Goldman, John -- Goh, Harriet -- Kim, Soo-Hyun -- Kim, Dong-Wook -- Chuah, Charles -- Oehler, Vivian G -- Radich, Jerald P -- Jordan, Craig T -- Reya, Tannishtha -- AI067798/AI/NIAID NIH HHS/ -- CA122206/CA/NCI NIH HHS/ -- CA140371/CA/NCI NIH HHS/ -- CA18029/CA/NCI NIH HHS/ -- DK072234/DK/NIDDK NIH HHS/ -- DK63031/DK/NIDDK NIH HHS/ -- DP1 CA174422/CA/NCI NIH HHS/ -- DP1 OD006430/OD/NIH HHS/ -- DP1 OD006430-01/OD/NIH HHS/ -- DP1 OD006430-02/OD/NIH HHS/ -- DP1OD006430/OD/NIH HHS/ -- HL097767/HL/NHLBI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- R01 CA140371/CA/NCI NIH HHS/ -- R01 DK063031/DK/NIDDK NIH HHS/ -- R01 DK063031-01/DK/NIDDK NIH HHS/ -- R01 DK063031-01S1/DK/NIDDK NIH HHS/ -- R01 DK063031-02/DK/NIDDK NIH HHS/ -- R01 DK063031-03/DK/NIDDK NIH HHS/ -- R01 DK063031-04/DK/NIDDK NIH HHS/ -- R01 DK063031-05/DK/NIDDK NIH HHS/ -- R01 DK063031-06/DK/NIDDK NIH HHS/ -- R01 DK063031-07/DK/NIDDK NIH HHS/ -- R01 DK063031-07S1/DK/NIDDK NIH HHS/ -- R01 DK063031-08/DK/NIDDK NIH HHS/ -- R01 DK072234/DK/NIDDK NIH HHS/ -- R01 DK072234-01A1/DK/NIDDK NIH HHS/ -- R01 DK072234-02/DK/NIDDK NIH HHS/ -- R01 DK072234-03/DK/NIDDK NIH HHS/ -- R01 DK072234-04/DK/NIDDK NIH HHS/ -- R01 HL097767/HL/NHLBI NIH HHS/ -- R01 HL097767-01/HL/NHLBI NIH HHS/ -- R01 HL097767-02/HL/NHLBI NIH HHS/ -- T32 GM007184-33/GM/NIGMS NIH HHS/ -- U19 AI067798/AI/NIAID NIH HHS/ -- U19 AI067798-010006/AI/NIAID NIH HHS/ -- U19 AI067798-020006/AI/NIAID NIH HHS/ -- U19 AI067798-030006/AI/NIAID NIH HHS/ -- U19 AI067798-040006/AI/NIAID NIH HHS/ -- U19 AI067798-050006/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):765-8. doi: 10.1038/nature09171. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639863" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blast Crisis/genetics/metabolism/pathology ; *Cell Differentiation/genetics ; Disease Progression ; Fusion Proteins, bcr-abl/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/*metabolism/*pathology ; Membrane Proteins/biosynthesis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/biosynthesis/genetics/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Prognosis ; RNA-Binding Proteins/biosynthesis/genetics/*metabolism ; Receptor, Notch1/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-12-11
    Description: The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred to represent an ancient lake and preserve evidence of an environment that would have been suited to support a martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen, sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements; by inference, phosphorus is assumed to have been available. The environment probably had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grotzinger, J P -- Sumner, D Y -- Kah, L C -- Stack, K -- Gupta, S -- Edgar, L -- Rubin, D -- Lewis, K -- Schieber, J -- Mangold, N -- Milliken, R -- Conrad, P G -- DesMarais, D -- Farmer, J -- Siebach, K -- Calef, F 3rd -- Hurowitz, J -- McLennan, S M -- Ming, D -- Vaniman, D -- Crisp, J -- Vasavada, A -- Edgett, K S -- Malin, M -- Blake, D -- Gellert, R -- Mahaffy, P -- Wiens, R C -- Maurice, S -- Grant, J A -- Wilson, S -- Anderson, R C -- Beegle, L -- Arvidson, R -- Hallet, B -- Sletten, R S -- Rice, M -- Bell, J 3rd -- Griffes, J -- Ehlmann, B -- Anderson, R B -- Bristow, T F -- Dietrich, W E -- Dromart, G -- Eigenbrode, J -- Fraeman, A -- Hardgrove, C -- Herkenhoff, K -- Jandura, L -- Kocurek, G -- Lee, S -- Leshin, L A -- Leveille, R -- Limonadi, D -- Maki, J -- McCloskey, S -- Meyer, M -- Minitti, M -- Newsom, H -- Oehler, D -- Okon, A -- Palucis, M -- Parker, T -- Rowland, S -- Schmidt, M -- Squyres, S -- Steele, A -- Stolper, E -- Summons, R -- Treiman, A -- Williams, R -- Yingst, A -- MSL Science Team -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):1242777. doi: 10.1126/science.1242777. Epub 2013 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Geologic and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24324272" target="_blank"〉PubMed〈/a〉
    Keywords: Bays ; Carbon/analysis ; *Exobiology ; *Extraterrestrial Environment ; Geologic Sediments/analysis/classification ; Hydrogen/analysis ; Hydrogen-Ion Concentration ; Iron/analysis/chemistry ; *Mars ; Nitrogen/analysis ; Oxidation-Reduction ; Oxygen/analysis ; Phosphorus/analysis ; Salinity ; Sulfur/analysis/chemistry ; *Water
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-07-16
    Description: Gross inequities in disease burden between developed and developing countries are now the subject of intense global attention. Public and private donors have marshaled resources and created organizational structures to accelerate the development of new health products and to procure and distribute drugs and vaccines for the poor. Despite these encouraging efforts directed primarily from and funded by industrialized countries, sufficiency and sustainability remain enormous challenges because of the sheer magnitude of the problem. Here we highlight a complementary and increasingly important means to improve health equity: the growing ability of some developing countries to undertake health innovation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morel, Carlos M -- Acharya, Tara -- Broun, Denis -- Dangi, Ajit -- Elias, Christopher -- Ganguly, N K -- Gardner, Charles A -- Gupta, R K -- Haycock, Jane -- Heher, Anthony D -- Hotez, Peter J -- Kettler, Hannah E -- Keusch, Gerald T -- Krattiger, Anatole F -- Kreutz, Fernando T -- Lall, Sanjaya -- Lee, Keun -- Mahoney, Richard -- Martinez-Palomo, Adolfo -- Mashelkar, R A -- Matlin, Stephen A -- Mzimba, Mandi -- Oehler, Joachim -- Ridley, Robert G -- Senanayake, Pramilla -- Singer, Peter -- Yun, Mikyung -- New York, N.Y. -- Science. 2005 Jul 15;309(5733):401-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Technological Development in Health, Oswaldo Cruz Foundation (FIOCRUZ), Avenida Brasil 4365, Rio de Janeiro, RJ 21040-900, Brazil. morel@fiocruz.br〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16020723" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Research/economics ; Biotechnology ; *Delivery of Health Care/organization & administration ; Developed Countries ; *Developing Countries ; *Diffusion of Innovation ; Drug Industry ; Health Policy ; Humans ; International Cooperation ; Patents as Topic ; Private Sector ; Public Sector ; Publishing ; Technology Transfer
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-10-10
    Description: The landforms of northern Gale crater on Mars expose thick sequences of sedimentary rocks. Based on images obtained by the Curiosity rover, we interpret these outcrops as evidence for past fluvial, deltaic, and lacustrine environments. Degradation of the crater wall and rim probably supplied these sediments, which advanced inward from the wall, infilling both the crater and an internal lake basin to a thickness of at least 75 meters. This intracrater lake system probably existed intermittently for thousands to millions of years, implying a relatively wet climate that supplied moisture to the crater rim and transported sediment via streams into the lake basin. The deposits in Gale crater were then exhumed, probably by wind-driven erosion, creating Aeolis Mons (Mount Sharp).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grotzinger, J P -- Gupta, S -- Malin, M C -- Rubin, D M -- Schieber, J -- Siebach, K -- Sumner, D Y -- Stack, K M -- Vasavada, A R -- Arvidson, R E -- Calef, F 3rd -- Edgar, L -- Fischer, W F -- Grant, J A -- Griffes, J -- Kah, L C -- Lamb, M P -- Lewis, K W -- Mangold, N -- Minitti, M E -- Palucis, M -- Rice, M -- Williams, R M E -- Yingst, R A -- Blake, D -- Blaney, D -- Conrad, P -- Crisp, J -- Dietrich, W E -- Dromart, G -- Edgett, K S -- Ewing, R C -- Gellert, R -- Hurowitz, J A -- Kocurek, G -- Mahaffy, P -- McBride, M J -- McLennan, S M -- Mischna, M -- Ming, D -- Milliken, R -- Newsom, H -- Oehler, D -- Parker, T J -- Vaniman, D -- Wiens, R C -- Wilson, S A -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):aac7575. doi: 10.1126/science.aac7575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Geologic and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA. ; Department of Earth Science and Engineering, Imperial College London, London SW7 2AZ, UK. ; Malin Space Science Systems, Post Office Box 910148, San Diego, CA 92121, USA. ; Department of Earth and Planetary Sciences, University of California-Santa Cruz, Santa Cruz, CA 95064, USA. ; Department of Geological Sciences, Indiana University, Bloomington, IN 47405, USA. ; Department of Earth and Planetary Sciences, University of California-Davis, Davis, CA 95616, USA. ; Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA. ; Department of Earth and Planetary Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA. ; Astrogeology Science Center, U.S. Geological Survey, Flagstaff, AZ 86001, USA. ; Center for Earth and Planetary Studies, National Air and Space Museum, Smithsonian Institution, Washington, DC 20560, USA. ; Department of Earth and Planetary Sciences, University of Tennessee, Knoxville, TN 37996, USA. ; Department of Earth and Planetary Sciences, Johns Hopkins University, Baltimore, MD 21218, USA. ; Laboratoire Planetologie et Geodynamique de Nantes-Le Centre National de la Recherche, Unite Mixte de Recherche 6112 and Universite de Nantes, 44322 Nantes, France. ; Planetary Science Institute, Tucson, AZ 85719, USA. ; Department of Geology, Western Washington University, Bellingham, WA 98225, USA. ; Department of Space Sciences, NASA Ames Research Center, Moffett Field, CA 94035, USA. ; NASA Goddard Space Flight Center, Greenbelt, MD 20771, USA. ; Department of Earth and Planetary Science, University of California-Berkeley, Berkeley, CA 94720, USA. ; Laboratoire de Geologie de Lyon, Universite de Lyon, 69364 Lyon, France. ; Department of Geology and Geophysics, Texas A&M University, College Station, TX 77843, USA. ; Department of Physics, University of Guelph, Guelph, Ontario N1G 2W1, Canada. ; Department of Geosciences, Stony Brook University, Stony Brook, NY 11794-2100, USA. ; Department of Geological Sciences, University of Texas at Austin, Austin, TX 78712, USA. ; Astromaterials Research and Exploration Science Division, NASA Johnson Space Center, Houston, TX 77058, USA. ; Department of Geological Sciences, Brown University, Providence, RI 02912, USA. ; Institute of Meteoritics, University of New Mexico, Albuquerque, NM 87131 USA. ; LZ Technology, NASA Johnson Space Center, Houston, TX 77058, USA. ; Space Remote Sensing, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450214" target="_blank"〉PubMed〈/a〉
    Keywords: Climate ; Exhumation ; *Lakes ; *Mars ; Paleontology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2019-07-13
    Description: Telescopic observations and orbital images of the Moon reveal at least 75 lunar pyroclastic deposits (LPDs), interpreted as the products of explosive volcanic eruptions [1]. The deposits are understood to be composed primarily of sub-millimeter beads of basaltic composition, ranging from glassy to partially-crystallized [2]. Delano [3] documented 25 distinct pyroclastic bead compositions in lunar soil samples, with a range of FeO abundances from 16.5 - 24.7 wt%. Green glasses generally have lower FeO abundances and red, yellow, and orange glasses generally have higher FeO abundances. The current study employs data from the Diviner Lunar Radiometer Experiment onboard the Lunar Reconnaissance Orbiter (LRO) to derive the FeO compositions of glasses from unsampled lunar pyroclastic deposits. The pyroclastic glasses are the deepest-sourced and most primitive basalts on the Moon [4]. Recent analyses have documented the presence of water in these glasses, demonstrating that the lunar interior is considerably more volatile-rich than previously understood [5]. Experiments have shown that the iron-rich pyroclastic glasses release the highest percentage of oxygen of any Apollo soils, making these deposits promising lunar resources [6].
    Keywords: Geophysics
    Type: JSC-CN-25614 , 43rd Lunar aud Plauetary Science Conference; Mar 19, 2012 - Mar 23, 2012; The Woodlands, TX; United States
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  • 6
    Publication Date: 2019-07-13
    Description: Several features in a high thermal inertia (TI) unit at Gale crater can be interpreted within a periglacial framework. These features include polygonally fractured terrain (cf. ice-wedge polygons), circumferential patterns of polygonal fractures (cf. relict pingos with ice-wedge polygons on their surfaces), irregularly-shaped and clustered depressions (cf. remnants of collapsed pingos and ephemeral lakes), and a general hummocky topography (cf. thermokarst). This interpretation would imply a major history of water and ice in Gale crater, involving permafrost, freeze-thaw cycles, and perhaps ponded surface water.
    Keywords: Geophysics
    Type: JSC-CN-27828 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 7
    Publication Date: 2019-07-13
    Description: Mud volcanoes provide a unique low-temperature window into the Earth s subsurface - including the deep biosphere - and may prove to be significant sources of atmospheric methane. The identification of analogous features on Mars would provide an important new class of sites for geological and astrobiological exploration. We report new work suggesting that features in Acidalia Planitia are most consistent with their being mud volcanoes.
    Keywords: Geophysics
    Type: JSC-17637 , 40th Lunar Planetary Conference; Mar 23, 2009 - Mar 27, 2009; Texas; United States
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  • 8
    Publication Date: 2019-07-13
    Description: The regional setting of the Chryse-Acidalia area augurs well for a fluid-rich subsurface, accumulation of diverse rock types reflecting the wide catchment area, astrobiological prospectivity, and mud volcanism. This latter provides a mechanism for transporting samples from relatively great depth to the surface. Since mud volcanoes are not associated with extreme heat or shock pressures, materials they transport to the surface are likely to be relatively unaltered; thus such materials could contain interpretable remnants of potential martian life (e.g., organic chemical biomarkers, mineral biosignatures, or structural remains) as well as unmetamorphosed rock samples. None of the previous landings on Mars was located in an area with features identified as potential mud volcanoes (Fig. 3), but some of these features may offer targets for future missions aimed at sampling deep fluid-rich strata with potential habitable zones.
    Keywords: Geophysics
    Type: JSC-17609 , 40th Lunar Planetary Conference; Mar 23, 2009 - Mar 27, 2009; Texas; United States
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  • 9
    Publication Date: 2019-07-13
    Description: Hydrothermal spring deposits on Mars would make excellent candidates for sample return. Molecular phylogeny suggests that that life on Earth may have arisen in hydrothermal settings [1-3], and on Mars, such settings not only would have supplied energy-rich waters in which martian life may have evolved [4-7] but also would have provided warm, liquid water to martian life forms as the climate became colder and drier [8]. Since silica, sulfates, and clays associated with hydrothermal settings are known to preserve geochemical and morphological remains of ancient terrestrial life [9-11], such settings on Mars might similarly preserve evidence of martian life. Finally, because formation of hydrothermal springs includes surface and subsurface processes, martian spring deposits would offer the potential to assess astrobiological potential and hydrological history in a variety of settings, including surface mineralized terraces, associated stream deposits, and subsurface environments where organic remains may have been well protected from oxidation. Previous attempts to identify martian spring deposits from orbit have been general or limited by resolution of available data [12-14]. However, new satellite imagery from HiRISE has a resolution of 28 cm/pixel, and based on these new data, we have interpreted several features in Vernal Crater, Arabia Terra as ancient hydrothermal springs [15, 16].
    Keywords: Geophysics
    Type: Ground Truth from Mars: Science Payoff; Apr 21, 2008 - Apr 23, 2008; Albuquerque, NM; United States
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  • 10
    Publication Date: 2019-07-13
    Description: Acidalia Planitia is a approx.3000 km diameter planum located in the northern plains of Mars. It is believed to be a sedimentary basin containing an accumulation of sediments brought by Hesperian outflow channels that drained the Highlands. A large number of high-albedo mounds have been identified across this basin [1-2] and understanding the process that formed them should help us understand the history of this region. Farrand et al. [2] showed that the mounds are dark in THEMIS (Thermal Emission Imaging System) nighttime IR (infrared) image data. This implies that the mounds have a lower thermal inertia than the surrounding plains (Fig. 1), suggesting that the material of the mounds is fine-grained or unconsolidated. Farrand et al. [2] also reviewed potential analogs for the mounds and concluded that a combination of mud volcanoes with evaporites around geysers or springs is most consistent with all the data. We have built on this work by creating regional maps of the features and analyzing CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) data to see if there are mineralogical differences between the mounds and surrounding plains.
    Keywords: Geophysics
    Type: JSC-CN-19978 , 41st Lunar and Planetary Science Conference; Mar 01, 2010 - Mar 05, 2010; The Woodlands, TX; United States
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