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  • 1
    Publication Date: 2011-03-16
    Description: Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2015-05-16
    Description: In porous media, the nonwetting phase is trapped on water saturation due to capillary forces acting in a heterogeneous porous structure. Within the capillary fringe, the gas phase is trapped and released along with the fluctuation of the water table, creating a highly active zone for biological transformations and mass transport. We conducted column experiments to observe and quantify the magnitude and structure of the trapped gas phase at the pore scale using computed microtomography. Different grain size distributions of glass beads were used to study the effect of the pore structure on trapping at various capillary numbers. Viscous forces were found to have negligible impact on phase trapping compared with capillary and buoyancy forces. Residual gas saturations ranged from 0.5 to 10%, while residual saturation increased with decreasing grain size. The gas phase was trapped by snap-off in single pores but also in pore clusters, while this single-pore trapping was dominant for grains larger than 1 mm in diameter. Gas surface area was found to increase linearly with increasing gas volume and with decreasing grain size.
    Electronic ISSN: 1539-1663
    Topics: Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 3
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    Springer
    In:  Berlin, Springer, vol. 10, no. Subvol. b, pp. 220, (ISBN: 0-08-037951-6)
    Publication Date: 1977
    Keywords: Textbook of physics
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  • 4
    Publication Date: 2019
    Description: Abstract Mineral dust is a key player in the Earth system that affects the weather and climate through absorbing and scattering the radiation. Such effects strongly depend on the optical properties of the particles that are in turn affected by the particle shape. For simplicity, dust particles are usually assumed to be spherical. But this assumption can lead to large errors in modeling and remote sensing applications. This study investigates the impact of dust particle shape on its direct radiative effect in a next‐generation atmospheric modeling system ICON‐ART (ICOsahedral Nonhydrostatic with Aerosols and Reactive Trace gases) to verify if accounting for non‐sphericity enhances the model‐observation agreement. Two sets of numerical experiments are conducted by changing the optical shape of the particles: one assuming spherical particles and the other one assuming a mixture of 35 randomly oriented tri‐axial ellipsoids. The simulations are compared to MISR, AERONET and CALIPSO observations (with focus on North Africa). The results show that consideration of particle non‐sphericity increases the dust AOD at 550 nm by up to 28% and leads to slight enhancement of the agreement between modeled and measured AOD. However, the model performance varies significantly when focusing on specific regions in North Africa. These differences stem from the uncertainties associated with particle size distribution and emission mechanisms in the model configuration. Regarding the attenuated backscatter, the simulated profile assuming non‐sphericity differs by a factor of 2 to 5 from the experiment assuming spherical dust, and is in a better agreement with the CALIPSO observations.
    Print ISSN: 2169-897X
    Electronic ISSN: 2169-8996
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
    Publication Date: 2017-07-14
    Description: Interest in energy storage technologies is still increasing in times of the excess of electricity that is generated by wind farms or solar plants. Solar electricity can be transformed to solar-hydrogen via water electrolysis. A crucial part of the energy storage technologies plays the efficient conversion of H 2 and CO 2 from renewable resources. Here, the process conditions for continuously catalytic hydrogenation of CO 2 to CH 3 OH under supercritical conditions over lab-synthesized Cu/ZnO/Al 2 O 3  catalysts were investigated. The impact of temperature (230 – 330 °C), residence time (0.5 - 2.2 s) at moderate pressure (150 bar) but even above the supercritical parameters of CO 2 showed a selective CO 2 hydrogenation. Higher H 2 concentrations, respectively higher H 2 :CO 2 -ratios (H 2 :CO 2  = 6), lead to an increased selectivity of CH 3 OH. A possible in situ phase separation of reaction products within the reactor due to the higher densities of the reaction mixture by the highered pressure could affect the kinectics and simplfy the down-stream processing. The combination of thermodynamic studies (phase separation phenomena) as well as the catalytic performance tests for the CO2 hydrogenation under supercritical conditions are discussed. Based on these data a process concept is presented.
    Print ISSN: 0930-7516
    Electronic ISSN: 1521-4125
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Published by Wiley
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  • 6
    Publication Date: 2011-08-13
    Description: Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537168/" 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/PMC3537168/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Star, Bastiaan -- Nederbragt, Alexander J -- Jentoft, Sissel -- Grimholt, Unni -- Malmstrom, Martin -- Gregers, Tone F -- Rounge, Trine B -- Paulsen, Jonas -- Solbakken, Monica H -- Sharma, Animesh -- Wetten, Ola F -- Lanzen, Anders -- Winer, Roger -- Knight, James -- Vogel, Jan-Hinnerk -- Aken, Bronwen -- Andersen, Oivind -- Lagesen, Karin -- Tooming-Klunderud, Ave -- Edvardsen, Rolf B -- Tina, Kirubakaran G -- Espelund, Mari -- Nepal, Chirag -- Previti, Christopher -- Karlsen, Bard Ove -- Moum, Truls -- Skage, Morten -- Berg, Paul R -- Gjoen, Tor -- Kuhl, Heiner -- Thorsen, Jim -- Malde, Ketil -- Reinhardt, Richard -- Du, Lei -- Johansen, Steinar D -- Searle, Steve -- Lien, Sigbjorn -- Nilsen, Frank -- Jonassen, Inge -- Omholt, Stig W -- Stenseth, Nils Chr -- Jakobsen, Kjetill S -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Aug 10;477(7363):207-10. doi: 10.1038/nature10342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ecological and Evolutionary Synthesis, Department of Biology, University of Oslo, PO Box 1066, Blindern, N-0316 Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21832995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Evolution, Molecular ; Gadus morhua/*genetics/*immunology ; Genome/*genetics ; Genomics ; Hemoglobins/genetics ; Immune System/*immunology ; Immunity/*genetics/immunology ; Major Histocompatibility Complex/genetics/immunology ; Male ; Polymorphism, Genetic/genetics ; Synteny/genetics ; Toll-Like Receptors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-08-15
    Description: CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192026/" 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/PMC4192026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Nostrand, Jeanine L -- Brady, Colleen A -- Jung, Heiyoun -- Fuentes, Daniel R -- Kozak, Margaret M -- Johnson, Thomas M -- Lin, Chieh-Yu -- Lin, Chien-Jung -- Swiderski, Donald L -- Vogel, Hannes -- Bernstein, Jonathan A -- Attie-Bitach, Tania -- Chang, Ching-Pin -- Wysocka, Joanna -- Martin, Donna M -- Attardi, Laura D -- 1F31CA167917-01/CA/NCI NIH HHS/ -- F31 CA167917/CA/NCI NIH HHS/ -- R01 CA140875/CA/NCI NIH HHS/ -- R01 DC009410/DC/NIDCD NIH HHS/ -- R01 GM095555/GM/NIGMS NIH HHS/ -- R01 HL118087/HL/NHLBI NIH HHS/ -- R01HL121197/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 9;514(7521):228-32. doi: 10.1038/nature13585. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA (C.A.B.); Department of Medicine, University of Central Florida, Orlando, Florida 32827, USA (M.M.K.); Department of Emergency Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA (T.M.J.). ; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Otolaryngology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Departement de Genetique, Hopital Necker-Enfants Malades, APHP, 75015 Paris, France [2] Unite INSERM U1163, Universite Paris Descartes-Sorbonne Paris Cite, Institut Imagine, 75015 Paris, France. ; Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Department of Pediatrics, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119037" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple/genetics/*metabolism ; Alleles ; Animals ; Apoptosis/genetics ; CHARGE Syndrome/*genetics/*metabolism ; Cell Cycle Checkpoints/genetics ; Craniofacial Abnormalities/genetics/metabolism ; DNA-Binding Proteins/deficiency/genetics/metabolism ; Ear/abnormalities ; Embryo, Mammalian/abnormalities/metabolism ; Female ; Fibroblasts ; Gene Deletion ; Heterozygote ; Humans ; Male ; Mice ; Mutant Proteins/metabolism ; *Phenotype ; Promoter Regions, Genetic/genetics ; Tumor Suppressor Protein p53/*genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-08-15
    Description: Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hassaine, Gherici -- Deluz, Cedric -- Grasso, Luigino -- Wyss, Romain -- Tol, Menno B -- Hovius, Ruud -- Graff, Alexandra -- Stahlberg, Henning -- Tomizaki, Takashi -- Desmyter, Aline -- Moreau, Christophe -- Li, Xiao-Dan -- Poitevin, Frederic -- Vogel, Horst -- Nury, Hugues -- England -- Nature. 2014 Aug 21;512(7514):276-81. doi: 10.1038/nature13552. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2]. ; Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland. ; Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland. ; Architecture et Fonction des Macromolecules Biologiques, CNRS UMR 7257 and Universite Aix-Marseille, F-13288 Marseille, France. ; 1] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France. ; Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Unite de Dynamique Structurale des Macromolecules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119048" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Receptors, Serotonin, 5-HT3/*chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-01-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, H -- New York, N.Y. -- Science. 1995 Jan 27;267(5197):437.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7824939" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases/deficiency/genetics ; *Drama ; *Fear ; Humans ; *Literature, Modern ; Male ; Mice ; Mice, Knockout
    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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  • 10
    Publication Date: 2013-05-22
    Description: Nogo-A is an important axonal growth inhibitor in the adult and developing CNS. In vitro, Nogo-A has been shown to inhibit migration and cell spreading of neuronal and nonneuronal cell types. Here, we studied in vivo and in vitro effects of Nogo-A on vascular endothelial cells during angiogenesis of the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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