153 research outputs found
Biferroic YCrO3
YCrO3 which has a monoclinic structure, shows weak ferromagnetism below 140 K
(TN) and a ferroelectric transition at 473 K accompanied by hysteresis. We have
determined the structure and energetics of YCrO3 with ferromagnetic and
antiferromagnetic ordering by means of first-principles density functional
theory calculations, based on pseudopotentials and a plane wave basis. The
non-centrosymmetric monoclinic structure is found to be lower in energy than
the orthorhombic structure, supporting the biferroic nature of YCrO3.Comment: 16 pages including figure
Multiferroic nature of charge-ordered rare earth manganites
Charge-ordered rare earth manganites Nd0.5Ca0.5MnO3, La0.25Nd0.25Ca0.5MnO3,
Pr0.7Ca0.3MnO3 and Pr0.6Ca0.4MnO3 are found to exhibit dielectric constant
anomalies around the charge-ordering or the magnetic transition temperatures.
Magnetic fields have a marked effect on the dielectric properties, indicating
the presence of coupling between the magnetic and electrical order parameters.
The observation of magnetoferroelectricity in these manganites is in accord
with the recent theoretical predictions of Khomskii and coworkers
A supramolecular assembly mediates lentiviral DNA integration
Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors
Local structural changes in paramagnetic and charge ordered phases of Sm0.2Pr0.3Sr0.5MnO3: An EXAFS Study
Sm{0.5-x}Pr{x}Sr{0.5}MnO{3} exhibits variety of ground states as x is varied
from 0 to 0.5. At an intermediate doping of x = 0.3 a charge-ordered CE type
antiferromagnetic insulating (AFI) ground state is seen. The transition to this
ground state is from a paramagnetic insulating (PMI) phase through a
ferromagnetic metallic phase (FMM). Local structures in PMI and AFI phases of x
= 0.3 sample have been investigated using Pr K-edge and Sm K-edge Extended
X-ray Absorption Fine Structure (EXAFS). It can be seen that the tilting and
rotation of the MnO6 octahedra about the b-axis are responsible for the charge
ordered CE-type antiferromagnetic ground state at low temperatures. In addition
a shift in the position of the rare earth ion along the c-axis has to be
considered to account for observed distribution of bond distances around the
rare earth ion
Correction: Interactions of prototype foamy virus capsids with host cell polo-like kinases are important for efficient viral DNA integration.
[This corrects the article DOI: 10.1371/journal.ppat.1005860.]
A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crstallographic Fragment Screening of the Catalytic Core Domain
HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials. ALLINIs exhibit a multimodal mechanism of action by inducing aberrant IN multimerization during virion morphogenesis and by competing with IN for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection. However, quinoline-based ALLINIs impose a low genetic barrier for the evolution of resistant phenotypes, which highlights a need for discovery of second-generation inhibitors. Using crystallographic screening of a library of 971 fragments against the HIV-1 IN catalytic core domain (CCD) followed by a fragment expansion approach, we have identified thiophenecarboxylic acid derivatives that bind at the CCD-CCD dimer interface at the principal lens epithelium-derived growth factor (LEDGF)/p75 binding pocket. The most active derivative (5) inhibited LEDGF/p75-dependent HIV-1 IN activity in vitro with an IC50 of 72 μm and impaired HIV-1 infection of T cells at an EC50 of 36 μm. The identified lead compound, with a relatively small molecular weight (221 Da), provides an optimal building block for developing a new class of inhibitors. Furthermore, although structurally distinct thiophenecarboxylic acid derivatives target a similar pocket at the IN dimer interface as the quinoline-based ALLINIs, the lead compound, 5, inhibited IN mutants that confer resistance to quinoline-based compounds. Collectively, our findings provide a plausible path for structure-based development of second-generation ALLINIs
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation
Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APCMin/+ mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy
Temperature-Dependent Infrared Reflectivity Studies of Multiferroic TbMnO_{3}: Evidence for Spin-Phonon Coupling
We have measured near normal incidence far infrared (FIR) reflectivity
spectra of a single crystal of TbMnO3 from 10K to 300K in the spectral range of
50 cm to 700 cm. Fifteen transverse optic (TO) and longitudinal
optic (LO) modes are identified in the imaginary part of the dielectric
function () and energy loss function
Im(-1/()), respectively. Some of the observed phonon modes
show anomalous softening below the magnetic transition temperature T (~
46K). We attribute this anomalous softening to the spin-phonon coupling caused
by phonon modulation of the super-exchange integral between the Mn
spins. The effective charge of oxygen (Z) calculated using the measured
LO-TO splitting increases below T.Comment: 16 pages, 6 figures, 1 tabl
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