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  • National Academy of Sciences  (39)
  • American Association for the Advancement of Science (AAAS)  (4)
  • Paleontological Society
  • 2010-2014  (31)
  • 2005-2009  (13)
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  • 1
    Publication Date: 2012-10-03
    Description: An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca2+-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2014-02-26
    Description: Astronomers and physicists noticed centuries ago that visual spatial resolution is higher for dark than light stimuli, but the neuronal mechanisms for this perceptual asymmetry remain unknown. Here we demonstrate that the asymmetry is caused by a neuronal nonlinearity in the early visual pathway. We show that neurons driven by...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 3
    Publication Date: 2013-01-16
    Description: In complex materials, how correlation between charge, spin, and lattice affects the emergent phenomena remains unclear. The newly discovered iron-based high-temperature superconductors and related compounds present to the community a prototype family of materials, where interplay between charge, spin, and lattice degrees of freedom can be explored. With the occurrence...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 4
    Publication Date: 2012-06-27
    Description: Evolution of pest resistance reduces the efficacy of insecticidal proteins from Bacillus thuringiensis (Bt) used in sprays or in transgenic crops. Although several pests have evolved resistance to Bt crops in the field, information about the genetic basis of field-evolved resistance to Bt crops has been limited. In particular, laboratory-selected resistance to Bt toxin Cry1Ac based on recessive mutations in a gene encoding a toxin-binding cadherin protein has been identified in three major cotton pests, but previous work has not determined if such mutations are associated with field-selected resistance to Bt cotton. Here we show that the most common resistance alleles in field populations of cotton bollworm, Helicoverpa armigera, selected with Bt cotton in northern China, had recessive cadherin mutations, including the deletion mutation identified via laboratory selection. However, unlike all previously studied cadherin resistance alleles, one field-selected cadherin resistance allele conferred nonrecessive resistance. We also detected nonrecessive resistance that was not genetically linked with the cadherin locus. In field-selected populations, recessive cadherin alleles accounted for 75–84% of resistance alleles detected. However, most resistance alleles occurred in heterozygotes and 59–94% of resistant individuals carried at least one nonrecessive resistance allele. The results suggest that resistance management strategies must account for diverse resistance alleles in field-selected populations, including nonrecessive alleles.
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    Electronic ISSN: 1091-6490
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  • 5
    Publication Date: 2012-06-06
    Description: Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemic brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 immunoreactivity in the periinfarct region, and glypican- and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan- or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 6
    Publication Date: 2011-02-23
    Description: Point mutations of the NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream effects of mutant IDH1 and IDH2 proteins or of 2HG on cellular metabolism are unknown. We profiled 〉200 metabolites in human oligodendroglioma (HOG) cells to determine the effects of expression of IDH1 and IDH2 mutants. Levels of amino acids, glutathione metabolites, choline derivatives, and tricarboxylic acid (TCA) cycle intermediates were altered in mutant IDH1- and IDH2-expressing cells. These changes were similar to those identified after treatment of the cells with 2HG. Remarkably, N-acetyl-aspartyl-glutamate (NAAG), a common dipeptide in brain, was 50-fold reduced in cells expressing IDH1 mutants and 8.3-fold reduced in cells expressing IDH2 mutants. NAAG also was significantly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations. These metabolic changes provide clues to the pathogenesis of tumors associated with IDH gene mutations.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 7
    Publication Date: 2011-08-03
    Description: GPR56, an orphan G protein-coupled receptor (GPCR) from the family of adhesion GPCRs, plays an indispensable role in cortical development and lamination. Mutations in the GPR56 gene cause a malformed cerebral cortex in both humans and mice that resembles cobblestone lissencephaly, which is characterized by overmigration of neurons beyond the pial basement membrane. However, the molecular mechanisms through which GPR56 regulates cortical development remain elusive due to the unknown status of its ligand. Here we identify collagen, type III, alpha-1 (gene symbol Col3a1) as the ligand of GPR56 through an in vitro biotinylation/proteomics approach. Further studies demonstrated that Col3a1 null mutant mice exhibit overmigration of neurons beyond the pial basement membrane and a cobblestone-like cortical malformation similar to the phenotype seen in Gpr56 null mutant mice. Functional studies suggest that the interaction of collagen III with its receptor GPR56 inhibits neural migration in vitro. As for intracellular signaling, GPR56 couples to the Gα12/13 family of G proteins and activates RhoA pathway upon ligand binding. Thus, collagen III regulates the proper lamination of the cerebral cortex by acting as the major ligand of GPR56 in the developing brain.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 8
    Publication Date: 2008-11-01
    Description: The gene transient receptor potential-melastatin-like 7 (Trpm7) encodes a protein that functions as an ion channel and a kinase. TRPM7 has been proposed to be required for cellular Mg2+ homeostasis in vertebrates. Deletion of mouse Trpm7 revealed that it is essential for embryonic development. Tissue-specific deletion of Trpm7 in the T cell lineage disrupted thymopoiesis, which led to a developmental block of thymocytes at the double-negative stage and a progressive depletion of thymic medullary cells. However, deletion of Trpm7 in T cells did not affect acute uptake of Mg2+ or the maintenance of total cellular Mg2+. Trpm7-deficient thymocytes exhibited dysregulated synthesis of many growth factors that are necessary for the differentiation and maintenance of thymic epithelial cells. The thymic medullary cells lost signal transducer and activator of transcription 3 activity, which accounts for their depletion when Trpm7 is disrupted in thymocytes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605283/" 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/PMC2605283/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jin, Jie -- Desai, Bimal N -- Navarro, Betsy -- Donovan, Adriana -- Andrews, Nancy C -- Clapham, David E -- T32HL007572-20/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):756-60. doi: 10.1126/science.1163493.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974357" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD44/metabolism ; *Embryonic Development ; Gene Deletion ; Homeostasis ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Interleukin-2 Receptor alpha Subunit/metabolism ; *Lymphopoiesis ; Magnesium/*metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; STAT3 Transcription Factor/metabolism ; T-Lymphocytes/*cytology/immunology/*metabolism ; TRPM Cation Channels/genetics/*physiology ; Thymus Gland/*cytology
    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
    Publication Date: 2013-02-16
    Description: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" 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/PMC3586787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangjin -- Brostromer, Erik -- Xing, Dong -- Jin, Jianshi -- Chong, Shasha -- Ge, Hao -- Wang, Siyuan -- Gu, Chan -- Yang, Lijiang -- Gao, Yi Qin -- Su, Xiao-dong -- Sun, Yujie -- Xie, X Sunney -- DP1 OD000277/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 15;339(6121):816-9. doi: 10.1126/science.1229223.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413354" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Base Sequence ; Binding Sites ; DNA, B-Form/*chemistry ; DNA-Binding Proteins/*chemistry ; DNA-Directed RNA Polymerases/chemistry ; Escherichia coli/genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Bacterial ; Lac Repressors/chemistry ; Molecular Dynamics Simulation ; Nucleosomes/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Glucocorticoid/chemistry ; Transcription Factors/*chemistry ; Viral Proteins/chemistry
    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: 2007-09-22
    Description: Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613796/" 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/PMC2613796/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghedin, Elodie -- Wang, Shiliang -- Spiro, David -- Caler, Elisabet -- Zhao, Qi -- Crabtree, Jonathan -- Allen, Jonathan E -- Delcher, Arthur L -- Guiliano, David B -- Miranda-Saavedra, Diego -- Angiuoli, Samuel V -- Creasy, Todd -- Amedeo, Paolo -- Haas, Brian -- El-Sayed, Najib M -- Wortman, Jennifer R -- Feldblyum, Tamara -- Tallon, Luke -- Schatz, Michael -- Shumway, Martin -- Koo, Hean -- Salzberg, Steven L -- Schobel, Seth -- Pertea, Mihaela -- Pop, Mihai -- White, Owen -- Barton, Geoffrey J -- Carlow, Clotilde K S -- Crawford, Michael J -- Daub, Jennifer -- Dimmic, Matthew W -- Estes, Chris F -- Foster, Jeremy M -- Ganatra, Mehul -- Gregory, William F -- Johnson, Nicholas M -- Jin, Jinming -- Komuniecki, Richard -- Korf, Ian -- Kumar, Sanjay -- Laney, Sandra -- Li, Ben-Wen -- Li, Wen -- Lindblom, Tim H -- Lustigman, Sara -- Ma, Dong -- Maina, Claude V -- Martin, David M A -- McCarter, James P -- McReynolds, Larry -- Mitreva, Makedonka -- Nutman, Thomas B -- Parkinson, John -- Peregrin-Alvarez, Jose M -- Poole, Catherine -- Ren, Qinghu -- Saunders, Lori -- Sluder, Ann E -- Smith, Katherine -- Stanke, Mario -- Unnasch, Thomas R -- Ware, Jenna -- Wei, Aguan D -- Weil, Gary -- Williams, Deryck J -- Zhang, Yinhua -- Williams, Steven A -- Fraser-Liggett, Claire -- Slatko, Barton -- Blaxter, Mark L -- Scott, Alan L -- R01 AI048562/AI/NIAID NIH HHS/ -- R01 AI048562-09/AI/NIAID NIH HHS/ -- R01 LM006845/LM/NLM NIH HHS/ -- R01 LM006845-08/LM/NLM NIH HHS/ -- R01 LM007938/LM/NLM NIH HHS/ -- R01 LM007938-04/LM/NLM NIH HHS/ -- R15 ES013128/ES/NIEHS NIH HHS/ -- R15 ES013128-01/ES/NIEHS NIH HHS/ -- U01 AI048828/AI/NIAID NIH HHS/ -- U01-AI50903/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1756-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. GhedinE@dom.pitt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885136" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brugia malayi/*genetics/physiology ; Caenorhabditis/genetics ; Drosophila melanogaster/genetics ; Drug Resistance/genetics ; Filariasis/parasitology ; *Genome, Helminth ; Humans ; Molecular Sequence Data
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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