271 research outputs found
Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression
The metabolic adaptation of eukaryotic cells to hypoxia involves increasing dependence upon glycolytic adenosine triphosphate (ATP) production, an event with consequences for cellular bioenergetics and cell fate. This response is regulated at the transcriptional level by the hypoxia-inducible factor-1(HIF-1)-dependent transcriptional upregulation of glycolytic enzymes (GEs) and glucose transporters. However, this transcriptional upregulation alone is unlikely to account fully for the levels of glycolytic ATP produced during hypoxia. Here, we investigated additional mechanisms regulating glycolysis in hypoxia. We observed that intestinal epithelial cells treated with inhibitors of transcription or translation and human platelets (which lack nuclei and the capacity for canonical transcriptional activity) maintained the capacity for hypoxia-induced glycolysis, a finding which suggests the involvement of a nontranscriptional component to the hypoxia-induced metabolic switch to a highly glycolytic phenotype. In our investigations into potential nontranscriptional mechanisms for glycolytic induction, we identified a hypoxia-sensitive formation of complexes comprising GEs and glucose transporters in intestinal epithelial cells. Surprisingly, the formation of such glycolytic complexes occurs independent of HIF-1-driven transcription. Finally, we provide evidence for the presence of HIF-1α in cytosolic fractions of hypoxic cells which physically interacts with the glucose transporter GLUT1 and the GEs in a hypoxia-sensitive manner. In conclusion, we provide insights into the nontranscriptional regulation of hypoxia-induced glycolysis in intestinal epithelial cells.</p
Electrically driven spin excitation in a ferroelectric magnet DyMnO_3
Temperature (5--250 K) and magnetic field (0--70 kOe) variations of the
low-energy (1--10 meV) electrodynamics of spin excitations have been
investigated for a complete set of light-polarization configurations for a
ferroelectric magnet DyMnO by using terahertz time-domain spectroscopy. We
identify the pronounced absorption continuum (1--8 meV) with a peak feature
around 2 meV, which is electric-dipole active only for the light -vector
along the a-axis. This absorption band grows in intensity with lowering
temperature from the spin-collinear paraelectric phase above the ferroelectric
transition, but is independent of the orientation of spiral spin plane ( or
), as shown on the original (ferroelectric polarization)
phase as well as the magnetic field induced phase. The possible origin of this electric-dipole active band is argued in
terms of the large fluctuations of spins and spin-current.Comment: New version, 11 pages including colored 8 figure
Electric-field control of spin waves at room temperature in multiferroic BiFeO3
To face the challenges lying beyond current CMOS-based technology, new
paradigms for information processing are required. Magnonics proposes to use
spin waves to carry and process information, in analogy with photonics that
relies on light waves, with several advantageous features such as potential
operation in the THz range and excellent coupling to spintronics. Several
magnonic analog and digital logic devices have been proposed, and some
demonstrated. Just as for spintronics, a key issue for magnonics is the large
power required to control/write information (conventionally achieved through
magnetic fields applied by strip lines, or by spin transfer from large
spin-polarized currents). Here we show that in BiFeO3, a room-temperature
magnetoelectric material, the spin wave frequency (>600 GHz) can be tuned
electrically by over 30%, in a non-volatile way and with virtually no power
dissipation. Theoretical calculations indicate that this effect originates from
a linear magnetoelectric effect related to spin-orbit coupling induced by the
applied electric field. We argue that these properties make BiFeO3 a promising
medium for spin wave generation, conversion and control in future magnonics
architectures.Comment: 3 figure
Dielectric nonlinearity of relaxor ferroelectric ceramics at low ac drives
Dielectric nonlinear response of
(PbMgNbO)(PbTiO) (0.9PMN-0.1PT) relaxor
ceramics was investigated under different ac drive voltages. It was observed
that: (i) the dielectric permittivity is independent on ac field amplitude at
high temperatures; (ii) with increasing ac drive, the permittivity maximum
increases, and the temperature of the maximum shifts to lower temperature;
(iii) the nonlinear effect is weakened when the measurement frequency
increases. The influences of increasing ac drive were found to be similar to
that of decreasing frequency. It is believed that the dielectric nonlinearities
of relaxors at low drives can be explained by the phase transition theory of
ergodic space shrinking in succession. A Monte Carlo simulation was performed
on the flips of micro polarizations at low ac drives to verify the theory.Comment: Submitted to J. Phys.: Cond. Matte
The polarizability model for ferroelectricity in perovskite oxides
This article reviews the polarizability model and its applications to
ferroelectric perovskite oxides. The motivation for the introduction of the
model is discussed and nonlinear oxygen ion polarizability effects and their
lattice dynamical implementation outlined. While a large part of this work is
dedicated to results obtained within the self-consistent-phonon approximation
(SPA), also nonlinear solutions of the model are handled which are of interest
to the physics of relaxor ferroelectrics, domain wall motions, incommensurate
phase transitions. The main emphasis is to compare the results of the model
with experimental data and to predict novel phenomena.Comment: 55 pages, 35 figure
AMP-regulated protein kinase activity in the hearts of mice treated with low- or high-fat diet measured using novel LC–MS method
Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease
Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al
Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds
Background: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods: Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results: Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. Conclusions: This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors
Terahertz time-domain spectroscopy of electromagnons in multiferroic perovskite manganites
Recent spectroscopic studies at terahertz frequencies for a variety of
multiferroics endowed with both ferroelectric and magnetic orders have revealed
the possible emergence of a new collective excitation, frequently referred to
as electromagnon. It is magnetic origin, but becomes active in response to the
electric field component of light. Here we give an overview on our recent
advance in the terahertz time-domain spectroscopy of electromagnons or
electric-dipole active magnetic resonances, focused on perovskite
manganites--MnO ( denotes rare-earth ions). The respective electric
and magnetic contributions to the observed magnetic resonance are firmly
identified by the measurements of the light-polarization dependence using a
complete set of the crystal orientations. We extract general optical features
in a variety of the spin ordered phases, including the -type
antiferromagnetic, collinear spin ordered, and ferroelectric and
spiral spin ordered phases, which are realized by tuning the chemical
composition of , temperature, and external magnetic field. In addition to
the antiferromagnetic resonances of Mn ions driven by the magnetic field
component of light, we clarify that the electromagnon appears only for light
polarized along the a-axis even in the collinear spin ordered phase and grows
in intensity with evolution of the spiral spin order, but independent of the
direction of the spiral spin plane ( or ) or equivalently the direction
of the ferroelectric polarization ( or ). A possible origin of the observed magnetic resonances at terahertz
frequencies is discussed by comparing the systematic experimental data
presented here with theoretical considerations based on Heisenberg model.Comment: 19 pages including 15 figures and 2 tables; Invited Paper in Special
Issue on Terahertz Wave Photonics in J. Opt. Soc. Am. B (Accepted for
publication
Unintentional high density p-type modulation doping of a GaAs/AlAs core-multi-shell nanowire
Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of
considerable technological importance but remains a challenge due to the
amphoteric behavior of the dopant atoms. Here we show that placing a narrow
GaAs quantum well in the AlAs shell effectively getters residual carbon
acceptors leading to an \emph{unintentional} p-type doping. Magneto-optical
studies of such a GaAs/AlAs core multi-shell NW reveal quantum confined
emission. Theoretical calculations of NW electronic structure confirm quantum
confinement of carriers at the core/shell interface due to the presence of
ionized carbon acceptors in the 1~nm GaAs layer in the shell.
Micro-photoluminescence in high magnetic field shows a clear signature of
avoided crossings of the Landau level emission line with the Landau
level TO phonon replica. The coupling is caused by the resonant hole-phonon
interaction, which points to a large 2D hole density in the structure.Comment: just published in Nano Letters
(http://pubs.acs.org/doi/full/10.1021/nl500818k
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