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  • American Association for the Advancement of Science (AAAS)  (24)
  • International Union of Crystallography (IUC)  (11)
  • 1
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    Transcriptome and epigenome landscape of human cortical development modeled in organoids (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.〈/p〉
    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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  • 2
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    Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉Studies of drug resistance mostly characterize genetic mutation, and we know much less about phenotypic mechanisms of drug resistance, especially at a quantitative level. p53 is an important mediator of cellular response to chemotherapy, but even p53 wild-type cells vary in drug sensitivity for unclear reasons. Here, we elucidated a new resistance mechanism to a DNA-damaging chemotherapeutic through bimodal modulation of p53 activation dynamics. By combining single-cell imaging with computational modeling, we characterized a four-component regulatory module, which generates bimodal p53 dynamics through coupled feed-forward and feedback, and found that the inhibitory strength between ATM and Mdm2 determined the differential modular output between drug-sensitive and drug-resistant cancer cell lines. We further showed that the combinatorial inhibition of Mdm2 and Wip1 was an effective strategy to alter p53 dynamics in resistant cancer cells and sensitize their apoptotic response. Our results point to p53 pulsing as a potentially druggable mechanism that mediates chemoresistance.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    {μ-6,6′-Dimethoxy-2,2′-[propane-1,3-diylbis(nitrilomethylidyne)]diphenolato}dimethanoltrinitratonickel(II)europium(III) methanol disolvate (2012)
    International Union of Crystallography (IUC)
    Details
    Publication Date: 2012-04-28
    Description: The title dinuclear complex, [EuNi(C19H20N2O4)(NO3)3(CH3OH)2]·2CH3OH, is isostructural with its NiII/PrIII analogue. The NiII ion is coordinated by two O atoms and two N atoms of a Schiff base ligand and by two methanol molecules, forming a slightly distorted octahedral geometry. The EuIII ion is coordinated by six O atoms from three chelating nitrate ligands and four O atoms from a Schiff base ligand, forming a distorted bicapped square-antiprismatic environment. Intermolecular O—H...O hydrogen bonds connect complexes and methanol solvent molecules.
    Electronic ISSN: 1600-5368
    Topics: Chemistry and Pharmacology , Geosciences
    Published by International Union of Crystallography (IUC)
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  • 4
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    Poly[[μ7-l-cysteato(2−)]disodium] (2011)
    International Union of Crystallography (IUC)
    Details
    Publication Date: 2011-09-16
    Description: The title compound {systematic name: poly[[μ7-(2R)-2-amino-3-sulfonatopropanoato]disodium]}, [Na2(C3H5NO5S)]n, was obtained through solvent-thermal reaction of l-cysteic acid and aqueous sodium hydroxide. The monomer consists of two Na+ cations that are coordinated to the deprotonated amino acid. The latter acts as donor utilizing all available coordination sites, viz. the amino, the carboxylate and the sulfonate residues, so producing a monomeric framework in which the two coordinated Na+ ions have different coordination spheres and geometries. One of the Na+ ions has an O5 coordination sphere with a typical geometric arrangement, intermediate between trigonal–bipyramidal and square–pyramidal; all the O atoms from the amino acid (three from the sulfonate and two from the caboxylate residues) act as donors. The second Na+ ion is tetracoordinated within an NO3 coordination sphere. The Na+ ion binds to the amino N atom, to one of the O atom of the carboxylic residue and to two O atoms of the sulfonate group in a distorted tetrahedral arrangement. As the sulfonate O atoms bind to both Na+ ions, a three-dimensional polymeric framework is obtained.
    Electronic ISSN: 1600-5368
    Topics: Chemistry and Pharmacology , Geosciences
    Published by International Union of Crystallography (IUC)
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  • 5
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    Origin of giant negative piezoelectricity in a layered van der Waals ferroelectric (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Recent research on piezoelectric materials is predominantly devoted to enhancing the piezoelectric coefficient, but overlooks its sign, largely because almost all of them exhibit positive longitudinal piezoelectricity. The only experimentally known exception is ferroelectric polymer poly(vinylidene fluoride) and its copolymers, which condense via weak van der Waals (vdW) interaction and show negative piezoelectricity. Here we report quantitative determination of giant intrinsic negative longitudinal piezoelectricity and electrostriction in another class of vdW solids—two-dimensional (2D) layered ferroelectric CuInP〈sub〉2〈/sub〉S〈sub〉6〈/sub〉. With the help of single crystal x-ray crystallography and density-functional theory calculations, we unravel the atomistic origin of negative piezoelectricity in this system, which arises from the large displacive instability of Cu ions coupled with its reduced lattice dimensionality. Furthermore, the sizable piezoelectric response and negligible substrate clamping effect of the 2D vdW piezoelectric materials warrant their great potential in nanoscale, flexible electromechanical devices.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Temperature sensitivity of SOM decomposition governed by aggregate protection and microbial communities (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Temperature sensitivity (〈i〉Q〈/i〉〈sub〉10〈/sub〉) of soil organic matter (SOM) decomposition is a crucial parameter for predicting the fate of soil carbon (C) under global warming. However, our understanding of its regulatory mechanisms remains inadequate, which constrains its accurate parameterization in Earth system models and induces large uncertainties in predicting terrestrial C-climate feedback. Here, we conducted a long-term laboratory incubation combined with a two-pool model and manipulative experiments to examine potential mechanisms underlying the depth-associated 〈i〉Q〈/i〉〈sub〉10〈/sub〉 variations in active and slow soil C pools. We found that lower microbial abundance and stronger aggregate protection were coexisting mechanisms underlying the lower 〈i〉Q〈/i〉〈sub〉10〈/sub〉 in the subsoil. Of them, microbial communities were the main determinant of 〈i〉Q〈/i〉〈sub〉10〈/sub〉 in the active pool, whereas aggregate protection exerted more important control in the slow pool. These results highlight the crucial role of soil C stabilization mechanisms in regulating temperature response of SOM decomposition, potentially attenuating the terrestrial C-climate feedback.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Large plasticity in magnesium mediated by pyramidal dislocations (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Lightweight magnesium alloys are attractive as structural materials for improving energy efficiency in applications such as weight reduction of transportation vehicles. One major obstacle for widespread applications is the limited ductility of magnesium, which has been attributed to 〈f〉〈/f〉 dislocations failing to accommodate plastic strain. We demonstrate, using in situ transmission electron microscope mechanical testing, that 〈f〉〈/f〉 dislocations of various characters can accommodate considerable plasticity through gliding on pyramidal planes. We found that submicrometer-size magnesium samples exhibit high plasticity that is far greater than for their bulk counterparts. Small crystal size usually brings high stress, which in turn activates more 〈f〉〈/f〉 dislocations in magnesium to accommodate plasticity, leading to both high strength and good plasticity.〈/p〉
    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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  • 8
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    Structural identification of a hotspot on CFTR for potentiation (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo–electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)–approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds.〈/p〉
    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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  • 9
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    Poly[bis(μ2-pyridine-2,6-dicarboxylato)cobalt(II)disodium(I)] (2012)
    International Union of Crystallography (IUC)
    Details
    Publication Date: 2012-04-01
    Description: The title compound, [Na2Co(C7H3NO4)2]n, is isostructural with the nickel(II) analog. In the crystal structure, the Co cation is coordinated by two N atoms and four O atoms of two pyridine-2,6-dicarboxylate groups with a strongly distorted octahedral geometry. The Na cations are coordinated by six O atoms of pyridine-2,6-dicarboxylate anions in an irregular geometry. The bis(pyridine-2,6-dicarboxylato)cobalt complexes are connected by the sodium cations into a three-dimensional coordination network.
    Electronic ISSN: 1600-5368
    Topics: Chemistry and Pharmacology , Geosciences
    Published by International Union of Crystallography (IUC)
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  • 10
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    Chloridotetrakis(1-ethyl-1H-imidazole-κN3)copper(II) chloride monohydrate (2012)
    International Union of Crystallography (IUC)
    Details
    Publication Date: 2012-04-01
    Description: The title compound, [CuCl(C5H8N2)4]Cl·H2O, consists of a discrete [CuCl(Eim)4]+ cation (Eim is 1-ethyl-1H-imidazole), one Cl− anion and one water molecule. The CuII ion adopts a distorted square-pyramidal geometry. The basal coordination positions are occupied by the N atoms of the Eim ligands and the apical position is occupied by a Cl− anion. In the crystal structure, ions and water molecules form three-dimensional hydrogen-bond networks which stabilize the structure.
    Electronic ISSN: 1600-5368
    Topics: Chemistry and Pharmacology , Geosciences
    Published by International Union of Crystallography (IUC)
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