2,481 research outputs found
Anti-Inflammatory and Anti-Thrombogenic Properties of Arterial Elastic Laminae
Elastic laminae, an elastin-based, layered extracellular matrix structure in the media of arteries, can inhibit leukocyte adhesion and vascular smooth muscle cell proliferation and migration, exhibiting anti-inflammatory and anti-thrombogenic properties. These properties prevent inflammatory and thrombogenic activities in the arterial media, constituting a mechanism for the maintenance of the structural integrity of the arterial wall in vascular disorders. The biological basis for these properties is the elastin-induced activation of inhibitory signaling pathways, involving the inhibitory cell receptor signal regulatory protein α (SIRPα) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1). The activation of these molecules causes deactivation of cell adhesion- and proliferation-regulatory signaling mechanisms. Given such anti-inflammatory and anti-thrombogenic properties, elastic laminae and elastin-based materials have potential for use in vascular reconstruction
Quantum Information Approach to Bose-Einstein Condensate in a Tilted Double-Well System
We study the ground state properties of bosons in a tilted double-well
system. We use fidelity susceptibility to identify the possible ground state
transitions under different tilt values. For a very small tilt (for example
), two transitions are found. For a moderate tilt (for example
), only one transition is found. For a large tilt (for example
), no transition is found. We explain this by analyzing the spectrum
of the ground state. The quantum discord and total correlation of the ground
state under different tilts are also calculated to indicate those transitions.
In the transition region, both quantities have peaks decaying exponentially
with particle number . This means for a finite-size system the transition
region cannot be explained by the mean-field theory, but in the large- limit
it can be.Comment: 5 pages, 5 figures, slightly different from the published versio
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
Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.
BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection
Hepatic cell mobilization for protection against ischemic myocardial injury
The heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia–reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3−/− mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3
Quantum gates implementations in the separated ion-traps by fast laser pulses
An approach is proposed to implement the universal quantum gates between the
ions confined individually in the separated traps. Instead of the typical
adiabatic operations, performed for manipulating the ion-ion coupling, here the
switchable couplings between ions are implemented non-adiabatically by using
the fast laser pulses. Consequently, the desirable quantum gates between the
ions could be implemented by using only a series of laser pulses. The proposal
may be conveniently generalized to the quantum computation with the scalable
ion-traps.Comment: 10 pages, 3figure
The Euler Number of Bloch States Manifold and the Quantum Phases in Gapped Fermionic Systems
We propose a topological Euler number to characterize nontrivial topological
phases of gapped fermionic systems, which originates from the Gauss-Bonnet
theorem on the Riemannian structure of Bloch states established by the real
part of the quantum geometric tensor in momentum space. Meanwhile, the
imaginary part of the geometric tensor corresponds to the Berry curvature which
leads to the Chern number characterization. We discuss the topological numbers
induced by the geometric tensor analytically in a general two-band model. As an
example, we show that the zero-temperature phase diagram of a transverse field
XY spin chain can be distinguished by the Euler characteristic number of the
Bloch states manifold in a (1+1)-dimensional Bloch momentum space
A unique distant submillimeter galaxy with an X-ray-obscured radio-luminous active galactic nucleus
We present a multiwavelength study of an atypical submillimeter galaxy in the
GOODS-North field, with the aim to understand its physical properties of
stellar and dust emission, as well as the central AGN activity. Although it is
shown that the source is likely an extremely dusty galaxy at high redshift, its
exact position of submillimeter emission is unknown. With the new NOEMA
interferometric imaging, we confirm that the source is a unique dusty galaxy.
It has no obvious counterpart in the optical and even NIR images observed with
HST at lambda~<1.4um. Photometric-redshift analyses from both stellar and dust
SED suggest it to likely be at z~>4, though a lower redshift at z~>3.1 cannot
be fully ruled out (at 90% confidence interval). Explaining its unusual
optical-to-NIR properties requires an old stellar population (~0.67 Gyr),
coexisting with a very dusty ongoing starburst component. The latter is
contributing to the FIR emission, with its rest-frame UV and optical light
being largely obscured along our line of sight. If the observed fluxes at the
rest-frame optical/NIR wavelengths were mainly contributed by old stars, a
total stellar mass of ~3.5x10^11Msun would be obtained. An X-ray spectral
analysis suggests that this galaxy harbors a heavily obscured AGN with
N_H=3.3x10^23 cm^-2 and an intrinsic 2-10 keV luminosity of L_X~2.6x10^44
erg/s, which places this object among distant type 2 quasars. The radio
emission of the source is extremely bright, which is an order of magnitude
higher than the star-formation-powered emission, making it one of the most
distant radio-luminous dusty galaxies. The combined characteristics of the
galaxy suggest that the source appears to have been caught in a rare but
critical transition stage in the evolution of submillimeter galaxies, where we
are witnessing the birth of a young AGN and possibly the earliest stage of its
jet formation and feedback.Comment: 13 pages in printer format, 10 figures, 1 table, accepted for
publication in the A&
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