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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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    Supertetrahedral sulfide crystals with giant cavities and channels (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-02-19
    Description: Although aluminosilicates and metal phosphates can form porous open-framework materials such as zeolites, sulfide analogs usually form high-density phases because of the relatively small tetrahedral angle at sulfur atoms. One strategy to overcome this limitation is to use tetrahedral clusters as the building blocks to achieve porous sulfide-based networks. The preparation and crystal structures of two indium sulfide open frameworks (ASU-31 and ASU-32) built of supertetrahedral clusters around organic template and water guests are described. ASU-31, based on the sodalite-tetrahedrite network, contains cavities 25.6 angstroms in diameter, and ASU-32, based on the tetragonal CrB4 network, contains channels with a minimum diameter of 14.7 angstroms. The organic cations can be completely exchanged with sodium ions in aqueous solution at room temperature without degradation of the crystals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li -- Laine -- O'Keeffe -- Yaghi -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1145-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Supramolecular Design and Discovery Group, Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024236" 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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  • 3
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    Effects of working-memory training on striatal dopamine release (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-08-06
    Description: Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Backman, Lars -- Nyberg, Lars -- Soveri, Anna -- Johansson, Jarkko -- Andersson, Micael -- Dahlin, Erika -- Neely, Anna S -- Virta, Jere -- Laine, Matti -- Rinne, Juha O -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):718. doi: 10.1126/science.1204978.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aging Research Center, Karolinska Institute, 171 77 Stockholm, Sweden. lars.backman.1@ki.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817043" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Corpus Striatum/*metabolism/radionuclide imaging ; Dopamine/*metabolism ; Humans ; *Learning ; Male ; *Memory, Short-Term ; Positron-Emission Tomography ; Raclopride/metabolism ; Receptors, Dopamine D2/*metabolism ; Young Adult
    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
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    Disease ecology. Ecological and evolutionary effects of fragmentation on infectious disease dynamics (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-06-14
    Description: Ecological theory predicts that disease incidence increases with increasing density of host networks, yet evolutionary theory suggests that host resistance increases accordingly. To test the combined effects of ecological and evolutionary forces on host-pathogen systems, we analyzed the spatiotemporal dynamics of a plant (Plantago lanceolata)-fungal pathogen (Podosphaera plantaginis)relationship for 12 years in over 4000 host populations. Disease prevalence at the metapopulation level was low, with high annual pathogen extinction rates balanced by frequent (re-)colonizations. Highly connected host populations experienced less pathogen colonization and higher pathogen extinction rates than expected; a laboratory assay confirmed that this phenomenon was caused by higher levels of disease resistance in highly connected host populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jousimo, Jussi -- Tack, Ayco J M -- Ovaskainen, Otso -- Mononen, Tommi -- Susi, Hanna -- Tollenaere, Charlotte -- Laine, Anna-Liisa -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1289-93. doi: 10.1126/science.1253621.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. ; Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. Department of Biomedical Engineering and Computational Science, Aalto University School of Science, FI-00076 Aalto, Finland. ; Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. anna-liisa.laine@helsinki.fi.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926021" target="_blank"〉PubMed〈/a〉
    Keywords: Ascomycota/*pathogenicity ; *Biological Evolution ; *Ecological and Environmental Processes ; Extinction, Biological ; *Host-Pathogen Interactions ; Plant Diseases/*microbiology ; Plantago/*microbiology ; Seasons
    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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  • 5
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    Eicosapentaenoic and Arachidonic Acids from Phytophthora infestans Elicit Fungitoxic Sesquiterpenes in the Potato (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-04-03
    Description: Mycelial extracts from Phytophthora infestans caused necrosis and elicited the accumulation of antimicrobial stress metabolites in potato tubers. A portion of the material with elicitor activity could be extracted from the mycelium by a mixture of chloroform and methanol. The most active elicitors of stress metabolites in these extracts were eicosapentaenoic and arachidonic acids. These fatty acids were found in either free or esterified form in all active fractions of the mycelial extracts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostock, R M -- Kuc, J A -- Laine, R A -- New York, N.Y. -- Science. 1981 Apr 3;212(4490):67-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17747631" 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
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  • 6
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    Evidence for a malarial parasite interaction site on the major transmembrane protein of the human erythrocyte (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-04-05
    Description: Soluble oligosaccharides derived from the surface of human erythrocytes were tested for their ability to competitively inhibit invasion of erythrocytes by Plasmodium falciparum, a malarial parasite. Invasion was most effectively inhibited by erythroglycan, a carbohydrate component of the band 3 transmembrane protein. The lactosamine chains of erythroglycan contributed much of the inhibitory activity. This indication of a primary parasite interaction site on band 3 supports a role for this protein in mediating the radical alterations of the erythrocyte cytoskeleton that accompany invasion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, M J -- Fukuda, M -- Laine, R A -- New York, N.Y. -- Science. 1985 Apr 5;228(4695):75-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3883494" target="_blank"〉PubMed〈/a〉
    Keywords: Anion Exchange Protein 1, Erythrocyte/*physiology ; Endocytosis ; Erythrocyte Membrane/*parasitology ; Humans ; Malaria/physiopathology ; Membrane Proteins/physiology ; Plasmodium falciparum/*physiology ; Spectrin/physiology
    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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    Recent natural selection causes adaptive evolution of an avian polygenic trait (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-10-20
    Description: We used extensive data from a long-term study of great tits ( Parus major ) in the United Kingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirm that these genes, especially the collagen gene COL4A5 , explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.
    Keywords: Evolution
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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