128 research outputs found
Magnetic Proximity Effect in Perovskite Superconductor/Ferromagnet Multilayers
superconducting/ferromagnetic
(SC/FM) multilayers have been studied by neutron reflectometry. Evidence for a
characteristic difference between the structural and magnetic depth profiles is
obtained from the occurrence of a structurally forbidden Bragg peak in the FM
state. The comparison with simulated reflectivity curves allows us to identify
two possible magnetization profiles: a sizable magnetic moment within the SC
layer antiparallel to the one in the FM layer (inverse proximity effect), or a
``dead'' region in the FM layer with zero net magnetic moment. The former
scenario is supported by an anomalous SC-induced enhancement of the
off-specular reflection, which testifies to a strong mutual interaction of SC
and FM order parameters.Comment: 4 pages, 2 figures, submitted to PR
Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development
Open Access funded by British Heart Foundation Under a Creative Commons license Acknowledgments Our thanks go to Gioia Polidori Francisco for training and discussions, Kate Watt and Yvonne Turnbull for technical and laboratory managerial support, Kadri Oras and Laura Ferguson for experimental support, Po-Lin So and Bruce Conklin (Gladstone Institutes) for providing their unpublished protocols, and Yukio Nakamura for discussion. This research is supported by the British Heart Foundation (PG/12/75/29851) and the Institute of Medical Sciences. A.S.B. was supported by the British Heart Foundation (FS/12/37/29516).Peer reviewedPublisher PD
X-ray study of structural domains in the near-surface region of SrTiOβ substrates with Y<sub>0.6</sub>Pr<sub>0.4</sub>BaβCuβOβ/La<sub>2/3</sub>Ca<sub>1/3</sub>MnOβ superlattices grown on top
We investigated with synchrotron x-ray diffraction and reflectometry the formation of structural domains in the near-surface region of single crystalline SrTiOβ (001) substrates with Y0.6Pr0.4BaβCuβOβ/La2/3Ca1/3MnOβ superlattices grown on top. We find that the antiferrodistortive cubic to tetragonal transition, which occurs at TSTO=104Β Β K in the bulk and at a considerably higher temperature of at least 120 K in the surface region of SrTiOβ, has only a weak influence on the domain formation. The strongest changes occur instead in the vicinity of the tetragonal to orthorhombic transition in SrTiOβ around 65 K where pronounced surface facets develop that reach deep (at least several micrometers) into the SrTiOβ substrate. These micrometer-sized facets are anisotropic and tilted with respect to one another by up to 0.5Β° along the shorter direction. Finally, we find that a third structural transition below 30 K gives rise to significant changes in the spread of the c-axis parameters. Overall, our data provide evidence for a strong mutual interaction between the structural properties of the SrTiOβ surface and the multilayer grown on top
Long-range transfer of electron-phonon coupling in oxide superlattices
The electron-phonon interaction is of central importance for the electrical
and thermal properties of solids, and its influence on superconductivity,
colossal magnetoresistance, and other many-body phenomena in
correlated-electron materials is currently the subject of intense research.
However, the non-local nature of the interactions between valence electrons and
lattice ions, often compounded by a plethora of vibrational modes, present
formidable challenges for attempts to experimentally control and theoretically
describe the physical properties of complex materials. Here we report a Raman
scattering study of the lattice dynamics in superlattices of the
high-temperature superconductor and the
colossal-magnetoresistance compound that suggests
a new approach to this problem. We find that a rotational mode of the MnO
octahedra in experiences pronounced
superconductivity-induced lineshape anomalies, which scale linearly with the
thickness of the layers over a remarkably long range of
several tens of nanometers. The transfer of the electron-phonon coupling
between superlattice layers can be understood as a consequence of long-range
Coulomb forces in conjunction with an orbital reconstruction at the interface.
The superlattice geometry thus provides new opportunities for controlled
modification of the electron-phonon interaction in complex materials.Comment: 13 pages, 4 figures. Revised version to be published in Nature
Material
Mouse Cofactor of BRCA1 (Cobra1) Is Required for Early Embryogenesis
Negative elongation factor (NELF) is a four-subunit protein complex conserved from Drosophila to humans. In vitro biochemical and tissue culture-based studies have demonstrated an important role of NELF in controlling RNA polymerase II (Pol II) pausing in transcription. However, the physiological significance of NELF function is not clear due to the lack of any genetic systems for studying NELF.Here we show that disruption of the mouse B subunit of NELF (NELF-B), also known as cofactor of BRCA1 (Cobra1), causes inner cell mass (ICM) deficiency and embryonic lethality at the time of implantation. Consistent with the phenotype of the Cobra1 knockout (KO) embryos, knockdown of Cobra1 in mouse embryonic stem cells (ESCs) reduces the efficiency of colony formation and increases spontaneous differentiation. Cobra1-depleted ESCs maintain normal levels of Oct4, Nanog, and Sox2, master regulators of pluripotency in ESCs. However, knockdown of Cobra1 leads to precocious expression of developmental regulators including lymphoid enhancer-binding factor 1 (Lef1). Chromatin immunoprecipitation (ChIP) indicates that Cobra1 binds to the Lef1 promoter and modulates the abundance of promoter-bound RNA polymerase.Cobra1 is essential for early embryogenesis. Our findings also indicate that Cobra1 helps maintain the undifferentiated state of mESCs by preventing unscheduled expression of developmental genes
Dissecting Molecular Differences between Wnt Coreceptors LRP5 and LRP6
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) serve as Wnt co-receptors for the canonical Ξ²-catenin pathway. While LRP6 is essential for embryogenesis, both LRP5 and LRP6 play critical roles for skeletal remodeling, osteoporosis pathogenesis and cancer formation, making LRP5 and LRP6 key therapeutic targets for cancer and disease treatment. LRP5 and LRP6 each contain in the cytoplasmic domain five conserved PPPSPxS motifs that are pivotal for signaling and serve collectively as phosphorylation-dependent docking sites for the scaffolding protein Axin. However existing data suggest that LRP6 is more effective than LRP5 in transducing the Wnt signal. To understand the molecular basis that accounts for the different signaling activity of LRP5 and LRP6, we generated a series of chimeric receptors via swapping LRP5 and LRP6 cytoplasmic domains, LRP5C and LRP6C, and studied their Wnt signaling activity using biochemical and functional assays. We demonstrate that LRP6C exhibits strong signaling activity while LRP5C is much less active in cells. Recombinant LRP5C and LRP6C upon in vitro phosphorylation exhibit similar Axin-binding capability, suggesting that LRP5 and LRP6 differ in vivo at a step prior to Axin-binding, likely at receiving phosphorylation. We identified between the two most carboxyl PPPSPxS motifs an intervening βgap4β region that appears to account for much of the difference between LRP5C and LRP6C, and showed that alterations in this region are sufficient to enhance LRP5 PPPSPxS phosphorylation and signaling to levels comparable to LRP6 in cells. In addition we provide evidence that binding of phosphorylated LRP5 or LRP6 to Axin is likely direct and does not require the GSK3 kinase as a bridging intermediate as has been proposed. Our studies therefore uncover a new and important molecular tuning mechanism for differential regulation of LRP5 and LRP6 phosphorylation and signaling activity
The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification
Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a βgate-keeperβ for the correct temporal and spatial development of the neural crest
Effects of EpCAM overexpression on human breast cancer cell lines
<p>Abstract</p> <p>Background</p> <p>Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients.</p> <p>Methods</p> <p>In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/Ξ²-catenin pathway. To evaluate the accumulation of Ξ²-catenin in the nucleus, a subcellular fractionation assay was performed.</p> <p>Results</p> <p>For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578T<sup>EpCAM </sup>and MDA-MB-231<sup>EpCAM </sup>indicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of Γ-catenin for MDA-MB-231<sup>EpCAM </sup>but not Hs578T<sup>EpCAM </sup>cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression.</p> <p>Conclusions</p> <p>These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.</p
Modulation of the Ξ²-Catenin Signaling Pathway by the Dishevelled-Associated Protein Hipk1
BACKGROUND:Wnts are evolutionarily conserved ligands that signal through beta-catenin-dependent and beta-catenin-independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. METHODOLOGY:We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene activation, as demonstrated by beta-catenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. CONCLUSIONS:These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/beta-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation
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