The Kinase PDK1 Is Essential for B-Cell Receptor Mediated Survival Signaling

Phosphoinositide-dependent kinase 1 (PDK1) plays an important role in integrating the T cell antigen receptor (TCR) and CD28 signals to achieve efficient NF-κB activation. PDK1 is also an important regulator of T cell development, mediating pre-TCR induced proliferation signals. However, the role of PDK1 in B cell antigen receptor (BCR) signaling and B cell development remains largely unknown. In this study we provide genetic evidence supporting the role of PDK1 in B cell survival. We found PDK1 is required for BCR mediated survival in resting B cells, likely through regulation of Foxo activation. PDK1-dependent signaling to NF-κB is not crucial to resting B cell viability. However, PDK1 is necessary for triggering NF-κB during B cell activation and is required for activated B cell survival. Together these studies demonstrate that PDK1 is essential for BCR-induced signal transduction to Foxo and NF-κB and is indispensable for both resting and activated B cell survival

Next-to-Leading-Order QCD corrections to J/\psi(\Upsilon)+\gamma production at the LHC

In this work, we calculate the next-to-leading-order (NLO) QCD corrections to the process $p+p \to J/\psi + \gamma$ via the color-singlet mechanism at the LHC. The results show that the partial cross section ($p_t^{J/\psi}>$3GeV and $|y^{J/\psi,\gamma}|<$3) is enhanced by a factor of about 2.0, and the differential cross section can be enhanced by two orders of magnitude in the large transverse momentum region of $J/\psi$. Furthermore, the polarization of $J/\psi$ changes from transverse polarization at leading-order to longitudinal polarization at NLO. For the inclusive $J/\psi$ hadroproduction, it is known that the color-octet contributions are one order of magnitude larger than the color-singlet contribution, and the polarization distribution is dominated by the color-octet behavior at NLO. In contrast, for $J/\psi+\gamma$ production the color-singlet contribution is of the same order as the color-octet contribution, and the polarization distribution arises from both the color-singlet and color-octet. Therefore, measurements of $J/\psi$ production associated with a direct photon at the hadron collider could be an important supplement to testify the theoretical framework treating with the heavy quarkonium. In addition, an NLO QCD correction to $\Upsilon+\gamma$ production at the LHC is also presented in this paper.Comment: 13 pages, 6 figures, 1 tabl

Dynamically generated 0^+ heavy mesons in a heavy chiral unitary approach

In terms of the heavy chiral Lagrangian and the unitarized coupled-channel scattering amplitude, interaction between the heavy meson and the light pseudoscalar meson is studied. By looking for the pole of scattering matrix on an appropriate Riemann sheet, a $DK$ bound state $D_{s0}^*$ with the mass of $2.312\pm0.041$ GeV is found. This state can be associated as the narrow $D_{sJ}^*(2317)$ state found recently. In the same way, a $B{\bar K}$ bound state $B_{s0}^*$ is found, and its mass of $5.725\pm0.039$ GeV is predicted. The spectra of $D_0^*$ and $B_0^*$ with $I=1/2$ are further investigated. One broad and one narrow states are predicted in both charm and bottom sectors. The coupling constants and decay widths of the predicted states are also calculated.Comment: 15 pages, 1 figure. One numerical error in Eq.16 correcte

Pilot Study: Alteration of Deleted in Liver Cancer1 and Phosphorylated Focal Adhesion Kinase Y397 Cytoplasmic Expression and the Prognostic Value in Advanced Epithelial Ovarian Carcinoma

Background: Deletion in liver cancer gene (DLC1) and phosphorylated focal adhesion kinase (p-FAK) have recently been reported as metastasis-related genes. However, the roles and prognostic values of their expression in epithelial ovarian carcinomas (EOCs) remain unclear. Methods: The expression and prognostic value of DLC1 and p-FAK Y397 in EOC were evaluated by immunohistochemistry and multivariate analysis. Results: Low expression of DLC1 and high expression of p-FAK Y397 were found in the 76 cases of EOC. The expression of DLC1 and p-FAK Y397 were negatively correlated. Multivariate analysis showed that the combination of them was an independent prognostic marker of EOC (P = 0.0319). Conclusions: DLC1 and pFAK Y397 had an association with the clinicopathologic characteristics of EOC. Expression of neither of these genes was a prognostic factor alone, but the combination revealed a significant prognostic value in the 60 cases of advanced stage EOC

Distinct patterns of Internet and smartphone-related problems among adolescents by gender: Latent class analysis

Background and objectives The ubiquitous Internet connections by smartphones weakened the traditional boundaries between computers and mobile phones. We sought to explore whether smartphone-related problems differ from those of computer use according to gender using latent class analysis (LCA). Methods After informed consents, 555 Korean middle-school students completed surveys on gaming, Internet use, and smartphone usage patterns. They also completed various psychosocial instruments. LCA was performed for the whole group and by gender. In addition to ANOVA and χ2 tests, post-hoc tests were conducted to examine differences among the LCA subgroups. Results In the whole group (n = 555), four subtypes were identified: dual-problem users (49.5%), problematic Internet users (7.7%), problematic smartphone users (32.1%), and “healthy” users (10.6%). Dual-problem users scored highest for addictive behaviors and other psychopathologies. The gender-stratified LCA revealed three subtypes for each gender. With dual-problem and healthy subgroup as common, problematic Internet subgroup was classified in the males, whereas problematic smartphone subgroup was classified in the females in the gender-stratified LCA. Thus, distinct patterns were observed according to gender with higher proportion of dual-problem present in males. While gaming was associated with problematic Internet use in males, aggression and impulsivity demonstrated associations with problematic smartphone use in females. Conclusions An increase in the number of digital media-related problems was associated with worse outcomes in various psychosocial scales. Gaming may play a crucial role in males solely displaying Internet-related problems. The heightened impulsivity and aggression seen in our female problematic smartphone users requires further research

Moire superlattice effects in graphene/boron-nitride van der Waals heterostructures

Van der Waals heterostructures of graphene and hexagonal boron nitride feature a moir\'e superlattice for graphene's Dirac electrons. Here, we review the effects generated by this superlattice, including a specific miniband structure featuring gaps and secondary Dirac points, and a fractal spectrum of magnetic minibands known as Hofstadter's butterfly.Comment: 25 pages, 7 figure

Singularities in Horava-Lifshitz theory

Singularities in $(3+1)$-dimensional Horava-Lifshitz (HL) theory of gravity are studied. These singularities can be divided into scalar, non-scalar curvature, and coordinate singularities. Because of the foliation-preserving diffeomorphisms of the theory, the number of scalars that can be constructed from the extrinsic curvature tensor $K_{ij}$, the 3-dimensional Riemann tensor and their derivatives is much large than that constructed from the 4-dimesnional Riemann tensor and its derivatives in general relativity (GR). As a result, even for the same spacetime, it may be singular in the HL theory but not in GR. Two representative families of solutions with projectability condition are studied, one is the (anti-) de Sitter Schwarzschild solutions, and the other is the Lu-Mei-Pope (LMP) solutions written in a form satisfying the projectability condition - the generalized LMP solutions. The (anti-) de Sitter Schwarzschild solutions are vacuum solutions of both HL theory and GR, while the LMP solutions with projectability condition satisfy the HL equations coupled with an anisotropic fluid with heat flow. It is found that the scalars $K$ and $K_{ij}K^{ij}$ are singular only at the center for the de Sitter Schwarzschild solution, but singular at both the center and $r = (3M/|\Lambda|)^{1/3}$ for the anti-de Sitter Schwarzschild solution. The singularity at $r = (3M/|\Lambda|)^{1/3}$ is absent in GR. In addition, all the generalized LMP solutions have two scalar curvature singularities, located at either $r = 0$ and $r=r_{s} > 0$, or $r=r_{1}$ and $r= r_{2}$ with $r_{2} > r_{1} > 0$, or $r=r_{s} > 0$ and $r = \infty$, depending on the choice of the free parameter $\lambda$.Comment: Revtex4, six figures. Version to appear in Phys. Lett.

Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis

Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β). TGF-β-deficient Treg cells were not able to regulate MDSC function in an experimentally induced model of colitis. Finally, we evaluated the therapeutic effect of TGF-β-mediated in-vitro-differentiated MDSCs on colitis. Adoptive transfer of MDSCs that differentiated with TGF-β led to better colitis prevention than the transfer of MDSCs that differentiated without TGF-β. Our results demonstrate an interaction between Treg cells and MDSCs that contributes to the regulation of MDSC proliferation and the acquisition of immunosuppressive functions

A Phenome-Based Functional Analysis of Transcription Factors in the Cereal Head Blight Fungus, Fusarium graminearum

Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. The fungus produces mycotoxins that are harmful to animal and human. In this study, a systematic analysis of 17 phenotypes of the mutants in 657 Fusarium graminearum genes encoding putative transcription factors (TFs) resulted in a database of over 11,000 phenotypes (phenome). This database provides comprehensive insights into how this cereal pathogen of global significance regulates traits important for growth, development, stress response, pathogenesis, and toxin production and how transcriptional regulations of these traits are interconnected. In-depth analysis of TFs involved in sexual development revealed that mutations causing defects in perithecia development frequently affect multiple other phenotypes, and the TFs associated with sexual development tend to be highly conserved in the fungal kingdom. Besides providing many new insights into understanding the function of F. graminearum TFs, this mutant library and phenome will be a valuable resource for characterizing the gene expression network in this fungus and serve as a reference for studying how different fungi have evolved to control various cellular processes at the transcriptional level

Effects of Astragalus Polysaccharide on Immune Responses of Porcine PBMC Stimulated with PRRSV or CSFV

BACKGROUND: Astragalus polysaccharide (APS) has been used as an immunomodulator that can enhance immune responses, whereas the immunomodulatory effects of APS on porcine peripheral blood mononuclear cells (PBMCs) exposed to porcine reproductive and respiratory syndrome virus (PRRSV) and classical swine fever virus (CSFV) have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: Porcine PBMCs were cultured in complete RPMI media in the presence of the R98-strain of PRRSV (5×10(4) TCID(50)/ml) or C-strain of CSFV (10(3) TCID(50)/ml) with or without APS. The expression of mRNA for CD28, cytotoxic T-lymphocyte antigen 4 (CTLA-4), transforming growth factor-β (TGF-β), interleukin 2 (IL-2) and IL-10 was assayed by TaqMan real-time RT-PCR. The expression of mRNA for CD28 and CTLA-4 increased at 24 h after stimulation of PBMCs with CSFV and the increased production of CTLA-4 was confirmed by western blot analysis, whereas the increases were inhibited by the addition of APS. In addition, APS alone upregulated IL-2 and TGF-β mRNA expression in PBMCs and the addition of APS had the capacity to prevent a further increase in IL-2 mRNA expression in PBMCs during CSFV or PRRSV infection, but had no effect on TGF-β mRNA expression. The production of tumor necrosis factor-alpha (TNF-α) increased at 12 h after stimulation with PRRSV or CSFV, but not with PRRSV plus APS or CSFV plus APS, whereas the addition of APS to PBMCs infected with PRRSV or CSFV promoted IL-10 mRNA expression. CONCLUSIONS: We suggested that APS had immunomodulatory effects on cells exposed to PRRSV or CSFV. It might be that APS via different mechanisms affects the activities of immune cells during either PRRSV or CSFV infection. This possibility warrants further studies to evaluate whether APS would be an effective adjuvant in vaccines against PRRSV or CSFV