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  • 1
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    Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-06-25
    Description: The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER + (estrogen receptor–positive)/PR + human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER + /PR + breast cancers should be explored.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    The 2018 rift eruption and summit collapse of Kilauea Volcano (2019)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2019
    Description: 〈p〉In 2018, Kīlauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu‘u ‘Ō‘ō vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 km. A 4 May earthquake (M6.9) produced ~5 m of fault slip. Lava erupted at rates exceeding 100 m〈sup〉3〈/sup〉/s, eventually covering 35.5 km〈sup〉2〈/sup〉. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M4.7-M5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent—about 0.8 km〈sup〉3〈/sup〉. Careful historical observation and monitoring of Kīlauea enabled successful forecasting of hazardous events.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    CMIP5 multimodel ensemble projection of storm track change under global warming (2013)
    Wiley
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    Publication Date: 2013-01-03
    Description: [1]  CMIP5 multimodel ensemble projection of midlatitude storm track changes has been examined. Storm track activity is quantified by temporal variance of meridional wind and sea level pressure (psl), as well as cyclone track statistics. For the Southern Hemisphere (SH), CMIP5 models project clear poleward migration, upward expansion, and intensification of the storm track. For the Northern Hemisphere (NH), the models also project some poleward shift and upward expansion of the storm track in the upper troposphere/lower stratosphere, but mainly weakening of the storm track toward its equatorward flank in the troposphere. Consistent with these, CMIP5 models project significant increase in the frequency of extreme cyclones during the SH cool season, but significant decrease in such events in the NH. Comparisons with CMIP3 projections indicate high degrees of consistency for SH projections, but significant differences are found in the NH. Overall, CMIP5 models project larger decrease in storm track activity in the NH troposphere, especially over North America in winter, where psl variance as well as cyclone frequency and amplitude are all projected to decrease significantly. In terms of climatology, similar to CMIP3, most CMIP5 models simulate storm tracks that are too weak and display equatorward biases in their latitude. These biases have also been related to future projections. In the NH, the strength of a model's climatological storm track is negatively correlated with its projected amplitude change under global warming, while in the SH, models with large equatorward biases in storm track latitude tend to project larger poleward shifts.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
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    Observed and projected decrease in Northern Hemisphere extratropical cyclone activity in summer and its impacts on maximum temperature (2016)
    Wiley
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    Publication Date: 2016-02-28
    Description: Extratropical cyclones cause much of the high impact weather over the mid-latitudes. With increasing greenhouse gases, enhanced high-latitude warming will lead to weaker cyclone activity. Here we show that between 1979 and 2014, the number of strong cyclones in Northern Hemisphere in summer has decreased at a rate of 4% per decade, with even larger decrease found near northeastern North America. Climate models project a decrease in summer cyclone activity, but the observed decreasing rate is near the fastest projected. Decrease in summer cyclone activity will lead to decrease in cloud cover, giving rise to higher maximum temperature, potentially enhancing the increase in maximum temperature by 0.5 K or more over some regions. We also show that climate models may have biases in simulating the positive relationship between cyclone activity and cloud cover, potentially under-estimating the impacts of cyclone decrease on accentuating the future increase in maximum temperature.
    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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  • 5
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    Impacts of Background Field Removal on CMIP5 Projected Changes in Pacific Winter Cyclone Activity (2013)
    Wiley
    Details
    Publication Date: 2013-12-11
    Description: [1]  Cyclones are responsible for much of the high impact weather in the extratropics, thus how they will change under global warming is of great concern. Several studies have used the multi-model climate simulations conducted under Phase 5 of the Coupled Model Intercomparison Project (CMIP5) to examine such changes. One study suggested that the frequency of strong cyclones is projected to decrease over the North Pacific, while another concluded that this frequency will increase. [2]  A single tracking algorithm has been used to derive cyclone statistics from 23 CMIP5 simulations using two different definitions of cyclones: cyclones as minima in total sea level pressure (SLP), or cyclones as minima in SLP perturbations about a large scale, low frequency background. When cyclones are defined by total SLP, the frequency of deep cyclones over the Pacific is projected to increase, while if cyclones are defined as perturbations, this frequency is projected to decrease. These differences are shown to be due to a projected deepening of the climatological mean Aleutian low. [3]  In view of these results, it is important to critically assess how cyclones should be defined. Preliminary results suggest that among CMIP5 simulations, over the Pacific, both the projected changes in the frequency of high wind events and mean available potential energy are better correlated with the projected changes in the frequency of cyclones defined as perturbations. It is concluded that more research should be done to quantify and understand the impacts of the different definitions of cyclones.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    The Kondo effect in an artificial quantum dot molecule (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-09-22
    Description: Double quantum dots provide an ideal model system for studying interactions between localized impurity spins. We report on the transport properties of a series-coupled double quantum dot as electrons are added one by one onto the dots. When the many-body molecular states are formed, we observe a splitting of the Kondo resonance peak in the differential conductance. This splitting reflects the energy difference between the bonding and antibonding states formed by the coherent superposition of the Kondo states of each dot. The occurrence of the Kondo resonance and its magnetic field dependence agree with a simple interpretation of the spin status of a double quantum dot.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jeong, H -- Chang, A M -- Melloch, M R -- New York, N.Y. -- Science. 2001 Sep 21;293(5538):2221-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11567130" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-11-16
    Description: Glycosylphosphatidylinositol (GPI) serves as a membrane anchor for a large number of eukaryotic proteins. A genetic approach was used to investigate the biosynthesis of GPI anchor precursors in mammalian cells. T cell hybridoma mutants that cannot synthesize dolichol-phosphate-mannose (Dol-P-Man) also do not express on their surface GPI-anchored proteins such as Thy-1 and Ly-6A. These mutants cannot form mannose-containing GPI precursors. Transfection with the yeast Dol-P-Man synthase gene rescues the synthesis of both Dol-P-Man and mannose-containing GPI precursors, as well as the surface expression of Thy-1 and Ly-6A, suggesting that Dol-P-Man is the donor of at least one mannose residue in the GPI core.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeGasperi, R -- Thomas, L J -- Sugiyama, E -- Chang, H M -- Beck, P J -- Orlean, P -- Albright, C -- Waneck, G -- Sambrook, J F -- Warren, C D -- AR-03564/AR/NIAMS NIH HHS/ -- HD-16942/HD/NICHD NIH HHS/ -- HD-21087/HD/NICHD NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Nov 16;250(4983):988-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1978413" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Ly/metabolism ; Antigens, Surface/metabolism ; Antigens, Thy-1 ; Cell Membrane/physiology ; Dolichol Monophosphate Mannose/metabolism ; *Genes, Fungal ; Glycolipids/*biosynthesis ; Glycosylphosphatidylinositols ; Hybridomas ; Phosphatidylinositols/*biosynthesis ; Rats ; Saccharomyces cerevisiae/genetics ; *Transfection
    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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  • 8
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    Cell signaling. Tel2 finally tells one story (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Michael -- Lingner, Joachim -- New York, N.Y. -- Science. 2008 Apr 4;320(5872):60-1. doi: 10.1126/science.1155132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecole Polytechnique Federale de Lausanne, Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges, Switzerland. michael.chang@epfl.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388281" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; DNA-Activated Protein Kinase/metabolism ; Humans ; Mice ; Nuclear Proteins/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases ; Telomere-Binding Proteins/genetics/*metabolism
    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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  • 9
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    Predicting human brain activity associated with the meanings of nouns (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-05-31
    Description: The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Tom M -- Shinkareva, Svetlana V -- Carlson, Andrew -- Chang, Kai-Min -- Malave, Vicente L -- Mason, Robert A -- Just, Marcel Adam -- New York, N.Y. -- Science. 2008 May 30;320(5880):1191-5. doi: 10.1126/science.1152876.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Machine Learning Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Tom.Mitchell@cs.cmu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18511683" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Brain/*physiology ; Brain Mapping ; Computational Biology ; Female ; Humans ; *Language ; Magnetic Resonance Imaging ; Male ; Models, Neurological ; Models, Statistical ; Semantics ; Speech Perception/*physiology
    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
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    Global mapping of the yeast genetic interaction network (2004)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2004-02-07
    Description: A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Amy Hin Yan -- Lesage, Guillaume -- Bader, Gary D -- Ding, Huiming -- Xu, Hong -- Xin, Xiaofeng -- Young, James -- Berriz, Gabriel F -- Brost, Renee L -- Chang, Michael -- Chen, YiQun -- Cheng, Xin -- Chua, Gordon -- Friesen, Helena -- Goldberg, Debra S -- Haynes, Jennifer -- Humphries, Christine -- He, Grace -- Hussein, Shamiza -- Ke, Lizhu -- Krogan, Nevan -- Li, Zhijian -- Levinson, Joshua N -- Lu, Hong -- Menard, Patrice -- Munyana, Christella -- Parsons, Ainslie B -- Ryan, Owen -- Tonikian, Raffi -- Roberts, Tania -- Sdicu, Anne-Marie -- Shapiro, Jesse -- Sheikh, Bilal -- Suter, Bernhard -- Wong, Sharyl L -- Zhang, Lan V -- Zhu, Hongwei -- Burd, Christopher G -- Munro, Sean -- Sander, Chris -- Rine, Jasper -- Greenblatt, Jack -- Peter, Matthias -- Bretscher, Anthony -- Bell, Graham -- Roth, Frederick P -- Brown, Grant W -- Andrews, Brenda -- Bussey, Howard -- Boone, Charles -- GM39066/GM/NIGMS NIH HHS/ -- GM61221/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):808-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764870" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Computational Biology ; Cystic Fibrosis/genetics ; Gene Deletion ; Genes, Essential ; *Genes, Fungal ; Genetic Diseases, Inborn/genetics ; Genotype ; Humans ; Molecular Sequence Data ; Multifactorial Inheritance ; Mutation ; Phenotype ; Polymorphism, Genetic ; Retinitis Pigmentosa/genetics ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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