Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection

PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Fluctuations of conserved charges at finite temperature from lattice QCD

We present the full results of the Wuppertal-Budapest lattice QCD collaboration on flavor diagonal and non-diagonal quark number susceptibilities with 2+1 staggered quark flavors, in a temperature range between 125 and 400 MeV. The light and strange quark masses are set to their physical values. Lattices with Nt=6, 8, 10, 12, 16 are used. We perform a continuum extrapolation of all observables under study. A Symanzik improved gauge and a stout-link improved staggered fermion action is utilized. All results are compared to the Hadron Resonance Gas model predictions: good agreement is found in the temperature region below the transition.Comment: 13 pages, 8 figures in Jhep styl

Effective interaction between molecules in the BEC regime of a superfluid Fermi gas

We investigate the effective interaction between Cooper-pair molecules in the st rong-coupling BEC regime of a superfluid Fermi gas with a Feshbach resonance. Our work uses a path integral formulation and a renormalization group (RG) analy sis of fluctuations in a single-channel model. We show that a physical cutoff en ergy $\omega_c$ originating from the finite molecular binding energy is the key to understanding the interaction between molecules in the BEC regime. Our work t hus clarifies recent results by showing that $a_{\rm M}=2a_{\rm F}$ is a {\it ba re} molecular scattering length while $a_{\rm M}=(0.6\sim0.75) a_{\rm F}$ is the low energy molecular scattering length renormalized to include high-energy scat tering up to $\omega_c$ (here $a_{\rm F}$ is the scattering length between Fermi atoms). We also include many-body effects at finite temperatures. We find that $a_{\rm M}$ is strongly dependent on temperature, vanishing at $T_{\rm c}$, consistent with the earlier Bose gas results of Bijlsma and Stoof.Comment: 10 pages, 3 figure

Universal time-dependent deformations of Schrodinger geometry

We investigate universal time-dependent exact deformations of Schrodinger geometry. We present 1) scale invariant but non-conformal deformation, 2) non-conformal but scale invariant deformation, and 3) both scale and conformal invariant deformation. All these solutions are universal in the sense that we could embed them in any supergravity constructions of the Schrodinger invariant geometry. We give a field theory interpretation of our time-dependent solutions. In particular, we argue that any time-dependent chemical potential can be treated exactly in our gravity dual approach.Comment: 24 pages, v2: references adde

A Kind of Affine Weighted Moment Invariants

A new kind of geometric invariants is proposed in this paper, which is called affine weighted moment invariant (AWMI). By combination of local affine differential invariants and a framework of global integral, they can more effectively extract features of images and help to increase the number of low-order invariants and to decrease the calculating cost. The experimental results show that AWMIs have good stability and distinguishability and achieve better results in image retrieval than traditional moment invariants. An extension to 3D is straightforward