Involvement of lipid rafts in adhesion-induced activation of Met and EGFR

<p>Abstract</p> <p>Background</p> <p>Cell adhesion has been shown to induce activation of certain growth factor receptors in a ligand-independent manner. However, the mechanism for such activation remains obscure.</p> <p>Methods</p> <p>Human epidermal carcinoma A431 cells were used as a model to examine the mechanism for adhesion-induced activation of hepatocyte growth factor receptor Met and epidermal growth factor receptor (EGFR). The cells were suspended and replated on culture dishes under various conditions. The phosphorylation of Met at Y1234/1235 and EGFR at Y1173 were used as indicators for their activation. The distribution of the receptors and lipid rafts on the plasma membrane were visualized by confocal fluorescent microscopy and total internal reflection microscopy.</p> <p>Results</p> <p>We demonstrate that Met and EGFR are constitutively activated in A431 cells, which confers proliferative and invasive potentials to the cells. The ligand-independent activation of Met and EGFR in A431 cells relies on cell adhesion to a substratum, but is independent of cell spreading, extracellular matrix proteins, and substratum stiffness. This adhesion-induced activation of Met and EGFR cannot be attributed to Src activation, production of reactive oxygen species, and the integrity of the cytoskeleton. In addition, we demonstrate that Met and EGFR are independently activated upon cell adhesion. However, partial depletion of Met and EGFR prevents their activation upon cell adhesion, suggesting that overexpression of the receptors is a prerequisite for their self-activation upon cell adhesion. Although Met and EGFR are largely distributed in 0.04% Triton-insoluble fractions (<it>i.e</it>. raft fraction), their activated forms are detected mainly in 0.04% Triton-soluble fractions (<it>i.e</it>. non-raft fraction). Upon cell adhesion, lipid rafts are accumulated at the cell surface close to the cell-substratum interface, while Met and EGFR are mostly excluded from the membrane enriched by lipid rafts.</p> <p>Conclusions</p> <p>Our results suggest for the first time that cell adhesion to a substratum may induce a polarized distribution of lipid rafts to the cell-substratum interface, which may allow Met and EGFR to be released from lipid rafts, thus leading to their activation in a ligand-independent manner.</p

The flavor-changing bottom-strange quark production in the littlest Higgs model with T parity at the ILC

In the littlest Higgs model with T-parity (LHT) the mirror quarks induce the special flavor structures and some new flavor-changing (FC) couplings which could greatly enhance the production rates of the FC processes. We in this paper study some bottom and anti-strange production processes in the LHT model at the International Linear Collider (ILC), i.e., $e^+e^-\rightarrow b\bar{s}$ and $\gamma\gamma\rightarrow b\bar{s}$. The results show that the production rates of these processes are sizeable for the favorable values of the parameters. Therefore, it is quite possible to test the LHT model or make some constrains on the relevant parameters of the LHT through the detection of these processes at the ILC.Comment: 12 pages, 8 figure

Presymptomatic change in microRNAs modulates Tau pathology.

MicroRNAs (miRs) are 18~23 nucleotides long non-coding RNAs that regulate gene expression. To explore whether miR alterations in tauopathy contribute to pathological conditions, we first determined which hippocampal miRs are altered at the presymptomatic and symptomatic stages of tauopathy using rTg4510 mice (Tau mice), a well-characterized tauopathy model. miR-RNA pairing analysis using QIAGEN Ingenuity Pathway Analysis (IPA) revealed 401 genes that can be regulated by 71 miRs altered in Tau hippocampi at the presymptomatic stage. Among several miRs confirmed with real-time qPCR, miR142 (-3p and -5p) in Tau hippocampi were significantly upregulated by two-weeks of age and onward. Transcriptome studies by RNAseq and IPA revealed several overlapping biological and disease associated pathways affected by either Tau or miR142 overexpression, including Signal Transducer and Activator of Transcription 3 (Stat3) and Tumor Necrosis Factor Receptor 2 (Tnfr2) signaling pathways. Similar to what was observed in Tau brains, overexpressing miR142 in wildtype cortical neurons augments mRNA levels of Glial Fibrillary Acidic Protein (Gfap) and Colony Stimulating Factor 1 (Csf1), accompanied by a significant increase in microglia and reactive astrocyte numbers. Taken together, our study suggests that miR alterations by Tau overexpression may contribute to the neuroinflammation observed in Tau brains

Fast simultaneous detection of K-RAS mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p><it>RAS </it>genes acquire the most common somatic gain-of-function mutations in human cancer, and almost all of these mutations are located at codons 12, 13, 61, and 146.</p> <p>Methods</p> <p>We present a method for detecting these <it>K-RAS </it>hotspot mutations in 228 cases of colorectal cancer. The protocol is based on the multiplex amplification of exons 2, 3 and 4 in a single tube, followed by primer extension of the PCR products using various sizes of primers to detect base changes at codons 12, 13, 61 and 146. We compared the clinicopathological data of colorectal cancer patients with the <it>K-RAS </it>mutation status.</p> <p>Results</p> <p><it>K-RAS </it>mutation occurred in 36% (83/228) of our colorectal cancer cases. Univariate analysis revealed a significant association between <it>K-RAS </it>mutation at codon 12 of exon 2 and poor 5-year survival (p = 0.023) and lymph node involvement (p = 0.048). Also, <it>K-RAS </it>mutation at codon 13 of exon 2 correlates with the size of the tumor (p = 0.03). Multivariate analysis adjusted for tumor size, histologic grade, and lymph node metastasis also indicated <it>K-RAS </it>mutations at codon 12 and 13 of exon 2 correlate significantly with overall survival (p = 0.002 and 0.025). No association was observed between codon 61 and 146 and clinicopathological features.</p> <p>Conclusion</p> <p>We demonstrated a simple and fast way to identify <it>K-RAS </it>mutation.</p

Quantum Interference between Impurities: Creating Novel Many-Body States in s-wave Superconductors

We demonstrate that quantum interference of electronic waves that are scattered by multiple magnetic impurities in an s-wave superconductor gives rise to novel bound states. We predict that by varying the inter-impurity distance or the relative angle between the impurity spins, the states' quantum numbers, as well as their distinct frequency and spatial dependencies, can be altered. Finally, we show that the superconductor can be driven through multiple local crossovers in which its spin polarization, $$, changes between $=0, 1/2$ and 1.Comment: 4 pages, 4 figure

B→KB\to K Transition Form Factor up to O(1/mb2){\cal O}(1/m^2_b) within the kTk_T Factorization Approach

In the paper, we apply the $k_T$ factorization approach to deal with the $B\to K$ transition form factor $F^{B\to K}_{+,0}(q^2)$ in the large recoil regions. The B-meson wave functions $\Psi_B$ and $\bar\Psi_B$ that include the three-particle Fock states' contributions are adopted to give a consistent PQCD analysis of the form factor up to ${\cal O} (1/m^2_b)$. It has been found that both the wave functions $\Psi_B$ and $\bar\Psi_B$ can give sizable contributions to the form factor and should be kept for a better understanding of the $B$ meson decays. Then the contributions from different twist structures of the kaon wavefunction are discussed, including the $SU_f(3)$-breaking effects. A sizable contribution from the twist-3 wave function $\Psi_p$ is found, whose model dependence is discussed by taking two group of parameters that are determined by different distribution amplitude moments obtained in the literature. It is also shown that $F^{B\to K}_{+,0}(0)=0.30\pm0.04$ and $[F^{B\to K}_{+,0}(0)/F^{B\to \pi}_{+,0}(0)]=1.13\pm0.02$, which are more reasonable and consistent with the light-cone sum rule results in the large recoil regions.Comment: 22 pages and 6 figure

Interplay of Mott Transition and Ferromagnetism in the Orbitally Degenerate Hubbard Model

A slave boson representation for the degenerate Hubbard model is introduced. The location of the metal to insulator transition that occurs at commensurate densities is shown to depend weakly on the band degeneracy M. The relative weights of the Hubbard sub-bands depend strongly on M, as well as the magnetic properties. It is also shown that a sizable Hund's rule coupling is required in order to have a ferromagnetic instability appearing. The metal to insulator transition driven by an increase in temperature is a strong function of it.Comment: 5 pages, revtex, 5 postscript figures, submitted to Phys. Rev.

New mechanism and improved kinetics of hydrogen absorption and desorption of Mg(In) solid solution alloy milling with CeF 3

Abstract(#br)This paper presents improving the hydrogen absorption and desorption of Mg(In) solid solution alloy through doped with CeF 3 . A nanocomposite of Mg 0.95 In 0.05 -5 wt% CeF 3 was prepared by mechanical ball milling. The microstructures were systematically investigated by X-ray diffraction, scanning electron microscopy, scanning transmission electron microscopy. And the hydrogen storage properties were evaluated by isothermal hydrogen absorption and desorption, and pressure-composition-isothermal measurements in a temperature range of 230 °C–320 °C. The mechanism of hydrogen absorption and desorption of Mg 0.95 In 0.05 solid solution is changed by the addition of CeF 3 . Mg 0.95 In 0.05 -5 wt% CeF 3 nanocomposite transforms to MgH 2 , MgF 2 and intermetallic compounds of MgIn and CeIn 3 by hydrogenation. Upon dehydrogenation, MgH 2 reacts with the intermetallic compounds of MgIn and CeIn 3 forming a pseudo-ternary Mg(In, Ce) solid solution, which is a fully reversible reaction with a reversible hydrogen capacity～4.0 wt%. The symbiotic nanostructured CeIn 3 impedes the agglomeration of MgIn compound, thus improving the dispersibility of element In, and finally improving the reversibility of hydrogen absorption and desorption of Mg(In) solution alloy. For Mg 0.95 In 0.05 -5 wt% CeF 3 nanocomposite, the dehydriding enthalpy is reduced to about 66.1 ± 3.2 kJ⋅mol −1 ⋅H 2 , and the apparent activation energy of dehydrogenation is significantly lowered to 71.9 ± 10.0 kJ⋅mol −1 ⋅H 2 , a reduction of ～73 kJ⋅mol −1 ⋅H 2 relative to that for Mg 0.95 In 0.05 solid solution. As a result, Mg 0.95 In 0.05 -5 wt% CeF 3 nanocomposite can release ～57% H 2 in 10 min at 260 °C. The improvements of hydrogen absorption and desorption properties are mainly attributed to the reversible phase transition of Mg(In, Ce) solid solution combing with the multiphase nanostructure

Exact soliton solution and inelastic two-soliton collision in spin chain driven by a time-dependent magnetic field

We investigate dynamics of exact N-soliton trains in spin chain driven by a time-dependent magnetic field by means of an inverse scattering transformation. The one-soliton solution indicates obviously the spin precession around the magnetic field and periodic shape-variation induced by the time varying field as well. In terms of the general soliton solutions N-soliton interaction and particularly various two-soliton collisions are analyzed. The inelastic collision by which we mean the soliton shape change before and after collision appears generally due to the time varying field. We, moreover, show that complete inelastic collisions can be achieved by adjusting spectrum and field parameters. This may lead a potential technique of shape control of soliton.Comment: 5 pages, 5 figure