Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection

Laser optical separation of chiral molecules

The optical trapping of molecules with an off-resonant laser beam involves a forward-Rayleigh scattering mechanism. It is shown that discriminatory effects arise on irradiating chiral molecules with circularly polarized light; the complete representation requires ensemble-weighted averaging to account for the influence of the trapping beam on the distribution of molecular orientations. Results of general application enable comparisons to be drawn between the results for two limits of the input laser intensity. It emerges that, in a racemic mixture, there is a differential driving force whose effect, at high laser intensities, is to produce differing local concentrations of the two enantiomers

Whole genome resequencing reveals signatures of selection and timing of duck domestication

Background The genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual. Results Our population and demographic analyses indicate a complex history of domestication, with early selection for separate meat and egg lineages. Genomic comparison of wild to domesticated populations suggest that genes affecting brain and neuronal development have undergone strong positive selection during domestication. Our FST analysis also indicates that the duck white plumage is the result of selection at the melanogenesis associated transcription factor locus. Conclusions Our results advance the understanding of animal domestication and selection for complex phenotypic traits

Line Defects in Molybdenum Disulfide Layers

Layered molecular materials and especially MoS2 are already accepted as promising candidates for nanoelectronics. In contrast to the bulk material, the observed electron mobility in single-layer MoS2 is unexpectedly low. Here we reveal the occurrence of intrinsic defects in MoS2 layers, known as inversion domains, where the layer changes its direction through a line defect. The line defects are observed experimentally by atomic resolution TEM. The structures were modeled and the stability and electronic properties of the defects were calculated using quantum-mechanical calculations based on the Density-Functional Tight-Binding method. The results of these calculations indicate the occurrence of new states within the band gap of the semiconducting MoS2. The most stable non-stoichiometric defect structures are observed experimentally, one of which contains metallic Mo-Mo bonds and another one bridging S atoms

Revisiting the Bs(∗)B^{(*)}_s-Meson Production at the Hadronic Colliders

The production of heavy-flavored hadron at the hadronic colliders provides a challenging opportunity to test the validity of pQCD predictions. There are two mechanisms for the $B^{(*)}_s$ hadroproduction, i.e. the gluon-gluon fusion mechanism via the subprocess $g+g\rightarrow B^{(*)}_s+b+\bar{s}$ and the extrinsic heavy quark mechanism via the subprocesses $g+\bar{b}\to B^{(*)}_s +\bar{s}$ and $g+s\to B^{(*)}_s +b$, both of which shall have sizable contributions in proper kinematic region. Different from the fixed-flavor-number scheme (FFNS) previously adopted in the literature, we study the $B^{(*)}_s$ hadroproduction under the general-mass variable-flavor-number scheme (GM-VFNS), in which we can consistently deal with the double counting problem from the above two mechanisms. Properties for the $B^{(*)}_s$ hadroproduction are discussed. To be useful reference, a comparative study of FFNS and GM-VFNS is presented. Both of which can provide reasonable estimations for the $B^{(*)}_s$ hadroproduction. At the Tevatron, the difference between these two schemes is small, however such difference is obvious at the LHC. The forthcoming more precise data on LHC shall provide a good chance to check which scheme is more appropriate to deal with the $B^{(*)}_s$-meson production and to further study the heavy quark components in hadrons.Comment: 18 pages, 8 figures, 4 tables. To match the published version. To be published in Eur.Phys.J.

Rapid Spread of Severe Fever with Thrombocytopenia Syndrome Virus by Parthenogenetic Asian Longhorned Ticks

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In Vivo Serial MR Imaging of Magnetically Labeled Endothelial Progenitor Cells Homing to the Endothelium Injured Artery in Mice

Background: Emerging evidence of histopathological analyses suggests that endothelial progenitor cells (EPCs) play an important role in vascular diseases. Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after vascular injury in mice. Therefore, it would be advantageous to develop an in vivo technique that can explore the temporal and spatial migration of EPCs homing to the damaged endothelium noninvasively. Methodology/Principal Findings: The left carotid common artery (LCCA) was injured by removal of endothelium with a flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen-derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to follow-up the injured artery at different time points after intravenous transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI. Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the labeled EPC transfusion group 15 days after LCCA injury, and it was found only in 1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC transfusion group were less than those of unlabeled EPC transfusion group and control group fifteen days after artery injury (p,0.05). Histopathological analyses confirmed accumulation and distribution of transfused EPCs at the injury site of LCCA. Conclusions/Significance: These data indicate that MR imaging might be used as an in vivo method for the tracking of EPC