34,419 research outputs found
SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D To Facilitate Viral Replication.
Accumulating evidence suggests that viruses hijack cellular proteins to circumvent the host immune system. Ubiquitination and SUMOylation are extensively studied posttranslational modifications (PTMs) that play critical roles in diverse biological processes. Cross talk between ubiquitination and SUMOylation of both host and viral proteins has been reported to result in distinct functional consequences. Enterovirus 71 (EV71), an RNA virus belonging to the family Picornaviridae, is a common cause of hand, foot, and mouth disease. Little is known concerning how host PTM systems interact with enteroviruses. Here, we demonstrate that the 3D protein, an RNA-dependent RNA polymerase (RdRp) of EV71, is modified by small ubiquitin-like modifier 1 (SUMO-1) both during infection and in vitro Residues K159 and L150/D151/L152 were responsible for 3D SUMOylation as determined by bioinformatics prediction combined with site-directed mutagenesis. Also, primer-dependent polymerase assays indicated that mutation of SUMOylation sites impaired 3D polymerase activity and virus replication. Moreover, 3D is ubiquitinated in a SUMO-dependent manner, and SUMOylation is crucial for 3D stability, which may be due to the interplay between the two PTMs. Importantly, increasing the level of SUMO-1 in EV71-infected cells augmented the SUMOylation and ubiquitination levels of 3D, leading to enhanced replication of EV71. These results together suggested that SUMO and ubiquitin cooperatively regulated EV71 infection, either by SUMO-ubiquitin hybrid chains or by ubiquitin conjugating to the exposed lysine residue through SUMOylation. Our study provides new insight into how a virus utilizes cellular pathways to facilitate its replication. IMPORTANCE: Infection with enterovirus 71 (EV71) often causes neurological diseases in children, and EV71 is responsible for the majority of fatalities. Based on a better understanding of interplay between virus and host cell, antiviral drugs against enteroviruses may be developed. As a dynamic cellular process of posttranslational modification, SUMOylation regulates global cellular protein localization, interaction, stability, and enzymatic activity. However, little is known concerning how SUMOylation directly influences virus replication by targeting viral polymerase. Here, we found that EV71 polymerase 3D was SUMOylated during EV71 infection and in vitro Moreover, the SUMOylation sites were determined, and in vitro polymerase assays indicated that mutations at SUMOylation sites could impair polymerase synthesis. Importantly, 3D is ubiquitinated in a SUMOylation-dependent manner that enhances the stability of the viral polymerase. Our findings indicate that the two modifications likely cooperatively enhance virus replication. Our study may offer a new therapeutic strategy against virus replication
Possible and Molecular states in a chiral quark model
We perform a systematic study of the bound state problem of and
systems by using effective interaction in our chiral quark model.
Our results show that both the interactions of and states
are attractive, which consequently result in
and bound states.Comment: arXiv admin note: substantial text overlap with arXiv:1204.395
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Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes.
Zika virus (ZIKV) infection in the human central nervous system (CNS) causes Guillain-Barre syndrome, cerebellum deformity, and other diseases. Astrocytes are immune response cells in the CNS and an important component of the blood-brain barrier. Consequently, any damage to astrocytes facilitates the spread of ZIKV in the CNS. Connective tissue growth factor/Nephroblastoma overexpressed gene family 1 (CCN1), an important inflammatory factor secreted by astrocytes, is reported to regulate innate immunity and viral infection. However, the mechanism by which astrocyte viral infection affects CCN1 expression remains undefined. In this study, we demonstrate that ZIKV infection up-regulates CCN1 expression in astrocytes, thus promoting intracellular viral replication. Other studies revealed that the cAMP response element (CRE) in the CCN1 promoter is activated by the ZIKV NS3 protein. The cAMP-responsive element-binding protein (CREB), a transacting factor of the CRE, is also activated by NS3 or ZIKV. Furthermore,a specific inhibitor of CREB, i.e. SGC-CBP30, reduced ZIKV-induced CCN1 up-regulation and ZIKV replication. Moreover, co-immunoprecipitation, overexpression, and knockdown studies confirmed that the interaction between NS3 and the regulatory domain of CaMKIIα could activate the CREB pathway, thus resulting in the up-regulation of CCN1 expression and enhancement of virus replication. In conclusion, the findings of our investigations on the NS3-CaMKIIα-CREB-CCN1 pathway provide a foundation for understanding the infection mechanism of ZIKV in the CNS
Search for via the transition at LHCb and factory
It is interesting to study the characteristics of the whole family of
which contains two different heavy flavors. LHC and the proposed factory
provide an opportunity because a large database on the family will be
achieved. and its excited states can be identified via their decay modes.
As suggested by experimentalists, is not easy to be
clearly measured, instead, the trajectories of and occurring in
the decay of () can be unambiguously
identified, thus the measurement seems easier and more reliable, therefore this
mode is more favorable at early running stage of LHCb and the proposed
factory. In this work, we calculate the rate of
in terms of the QCD multipole-expansion and the numerical results indicate that
the experimental measurements with the luminosity of LHC and factory are
feasible.Comment: 12 pages, 1 figures and 4 tables, acceptted by SCIENCE CHINA Physics,
Mechanics & Astronomy (Science in China Series G
ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells.
BACKGROUND: Many viruses depend on the extensive membranous network of the endoplasmic reticulum (ER) for their translation, replication, and packaging. Certain membrane modifications of the ER can be a trigger for ER stress, as well as the accumulation of viral protein in the ER by viral infection. Then, unfolded protein response (UPR) is activated to alleviate the stress. Zika virus (ZIKV) is a mosquito-borne flavivirus and its infection causes microcephaly in newborns and serious neurological complications in adults. Here, we investigated ER stress and the regulating model of UPR in ZIKV-infected neural cells in vitro and in vivo. METHODS: Mice deficient in type I and II IFN receptors were infected with ZIKV via intraperitoneal injection and the nervous tissues of the mice were assayed at 5 days post-infection. The expression of phospho-IRE1, XBP1, and ATF6 which were the key markers of ER stress were analyzed by immunohistochemistry assay in vivo. Additionally, the nuclear localization of XBP1s and ATF6n were analyzed by immunohistofluorescence. Furthermore, two representative neural cells, neuroblastoma cell line (SK-N-SH) and astrocytoma cell line (CCF-STTG1), were selected to verify the ER stress in vitro. The expression of BIP, phospho-elF2α, phospho-IRE1, and ATF6 were analyzed through western blot and the nuclear localization of XBP1s was performed by confocal immunofluorescence microscopy. RT-qPCR was also used to quantify the mRNA level of the UPR downstream genes in vitro and in vivo. RESULTS: ZIKV infection significantly upregulated the expression of ER stress markers in vitro and in vivo. Phospho-IRE1 and XBP1 expression significantly increased in the cerebellum and mesocephalon, while ATF6 expression significantly increased in the mesocephalon. ATF6n and XBP1s were translocated into the cell nucleus. The levels of BIP, ATF6, phospho-elf2α, and spliced xbp1 also significantly increased in vitro. Furthermore, the downstream genes of UPR were detected to investigate the regulating model of the UPR during ZIKV infection in vitro and in vivo. The transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of gadd34 and chop in vitro significantly increased. CONCLUSION: Findings in this study demonstrated that ZIKV infection activates ER stress in neural cells. The results offer clues to further study the mechanism of neuropathogenesis caused by ZIKV infection
On Silicon Carbide Grains as the Carrier of the 21 Micron Emission Feature in Post-Asymptotic Giant Branch Stars
The mysterious 21mu emission feature seen in 12 proto-planetary nebulae
(PPNe) remains unidentified since its first detection in 1989. Over a dozen of
candidate materials have been proposed within the past decade, but none of them
has received general acceptance. Very recently, silicon carbide (SiC) grains
with impurities were suggested to be the carrier of this enigmatic feature,
based on recent laboratory data that doped SiC grains exhibit a resonance at
\~21mu. This proposal gains strength from the fact that SiC is a common dust
species in carbon-rich circumstellar envelopes. However, SiC dust has a strong
vibrational band at ~11.3mu. We show in this Letter that in order to be
consistent with the observed flux ratios of the 11.3mu feature to the 21mu
feature, the band strength of the 21mu resonance has to be very strong, too
strong to be consistent with current laboratory measurements. But this does not
yet readily rule out the SiC hypothesis since recent experimental results have
demonstrated that the 21mu resonance of doped SiC becomes stronger as the C
impurity increases. Further laboratory measurements of SiC dust with high
fractions of C impurity are urgently needed to test the hypothesis of SiC as
the carrier of the 21mu feature.Comment: 14 pages, 3 figures, accepted for publication in ApJ
A Cosmology-Independent Calibration of Gamma-Ray Burst Luminosity Relations and the Hubble Diagram
An important concern in the application of gamma-ray bursts (GRBs) to
cosmology is that the calibration of GRB luminosity/energy relations depends on
the cosmological model, due to the lack of a sufficient low-redshift GRB
sample. In this paper, we present a new method to calibrate GRB relations in a
cosmology-independent way. Since objects at the same redshift should have the
same luminosity distance and since the distance moduli of Type Ia supernovae
(SNe Ia) obtained directly from observations are completely cosmology
independent, we obtain the distance modulus of a GRB at a given redshift by
interpolating from the Hubble diagram of SNe Ia. Then we calibrate seven GRB
relations without assuming a particular cosmological model and construct a GRB
Hubble diagram to constrain cosmological parameters. From the 42 GRBs at
, we obtain ,
for the flat CDM model, and
for the dark energy model with a constant equation of state
, which is consistent with the concordance model in
a 1- confidence region.Comment: 7 pages, 3 figures, 1 table, now matches the editorially revised
version; accepted for publication in ApJ (vol 685)
The magnetic dipole transitions in the binding system
The magnetic dipole transitions between the vector mesons and their
relevant pseudoscalar mesons (, , , ,
and etc, the binding states of system) of
the family are interesting. To see the `hyperfine' splitting due to
spin-spin interaction is an important topic for understanding the spin-spin
interaction and the spectrum of the the binding system. The
knowledge about the magnetic dipole transitions is also very useful for
identifying the vector boson mesons experimentally, whose masses are
just slightly above the masses of their relevant pseudoscalar mesons
accordingly. Considering the possibility to observe the vector mesons via the
transitions at factory and the potentially usages of the theoretical
estimate on the transitions, we fucus our efforts on calculating the magnetic
dipole transitions, i.e. precisely to calculate the rates for the transitions
such as decays and , and particularly
work in the Behte-Salpeter framework. In the estimate, as a typical example, we
carefully investigate the dependance of the rate
on the mass difference as well.Comment: 10 pages, 2 figures, 1 tabl
Large magnetothermal conductivity of HoMnO_3 single crystals and its relation to the magnetic-field induced transitions of magnetic structure
We study the low-temperature heat transport of HoMnO_3 single crystals to
probe the magnetic structures and their transitions induced by magnetic field.
It is found that the low-T thermal conductivity (\kappa) shows very strong
magnetic-field dependence, with the strongest suppression of nearly 90% and the
biggest increase of 20 times of \kappa compared to its zero-field value. In
particular, some ``dip"-like features show up in \kappa(H) isotherms for field
along both the ab plane and the c axis. These behaviors are found to shed new
light on the complex H-T phase diagram and the field-induced re-orientations of
Mn^{3+} and Ho^{3+} spin structures. The results also demonstrate a significant
spin-phonon coupling in this multiferroic compound.Comment: 5 pages, 4 figures, accepted for publication in Phys. Rev.
Different atmospheric moisture divergence responses to extreme and moderate El Niños
On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST
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