Neural regulation of cancer: from mechanobiology to inflammation.

Despite recent progress in cancer research, the exact nature of malignant transformation and its progression is still not fully understood. Particularly metastasis, which accounts for most cancer death, is a very complex process, and new treatment strategies require a more comprehensive understanding of underlying regulatory mechanisms. Recently, the sympathetic nervous system (SNS) has been implicated in cancer progression and beta-blockers have been identified as a novel strategy to limit metastasis. This review discusses evidence that SNS signaling regulates metastasis by modulating the physical characteristics of tumor cells, tumor-associated immune cells and the extracellular matrix (ECM). Altered mechanotype is an emerging hallmark of cancer cells that is linked to invasive phenotype and treatment resistance. Mechanotype also influences crosstalk between tumor cells and their environment, and may thus have a critical role in cancer progression. First, we discuss how neural signaling regulates metastasis and how SNS signaling regulates both biochemical and mechanical properties of tumor cells, immune cells and the ECM. We then review our current knowledge of the mechanobiology of cancer with a focus on metastasis. Next, we discuss links between SNS activity and tumor-associated inflammation, the mechanical properties of immune cells, and how the physical properties of the ECM regulate cancer and metastasis. Finally, we discuss the potential for clinical translation of our knowledge of cancer mechanobiology to improve diagnosis and treatment

Heating and Turbulence Driving by Galaxy Motions in Galaxy Clusters

Using three-dimensional hydrodynamic simulations, we investigate heating and turbulence driving in an intracluster medium (ICM) by orbital motions of galaxies in a galaxy cluster. We consider Ng member galaxies on isothermal and isotropic orbits through an ICM typical of rich clusters. An introduction of the galaxies immediately produces gravitational wakes, providing perturbations that can potentially grow via resonant interaction with the background gas. When Ng^{1/2}Mg_11 < 100, where Mg_11 is each galaxy mass in units of 10^{11} Msun, the perturbations are in the linear regime and the resonant excitation of gravity waves is efficient to generate kinetic energy in the ICM, resulting in the velocity dispersion sigma_v ~ 2.2 Ng^{1/2}Mg_11 km/s. When Ng^{1/2}Mg_11 > 100, on the other hand, nonlinear fluctuations of the background ICM destroy galaxy wakes and thus render resonant excitation weak or absent. In this case, the kinetic energy saturates at the level corresponding to sigma_v ~ 220 km/s. The angle-averaged velocity power spectra of turbulence driven in our models have slopes in the range of -3.7 to -4.3. With the nonlinear saturation of resonant excitation, none of the cooling models considered are able to halt cooling catastrophe, suggesting that the galaxy motions alone are unlikely to solve the cooling flow problem.Comment: 12 pages including 3 figures, To appear in ApJ

BFT Hamiltonian embedding for SU(3) Skyrmion

We newly apply the Batalin, Fradkin and Tyutin (BFT) formalism to the SU(3) flavor Skyrmion model to investigate the Weyl ordering correction to the structure of the hyperfine splittings of strange baryons. On the other hand, the Berry phases and Casimir effects are also discussed.Comment: 14 pages, modified titl

Local Hall effect in hybrid ferromagnetic/semiconductor devices

We have investigated the magnetoresistance of ferromagnet-semiconductor devices in an InAs two-dimensional electron gas system in which the magnetic field has a sinusoidal profile. The magnetoresistance of our device is large. The longitudinal resistance has an additional contribution which is odd in applied magnetic field. It becomes even negative at low temperature where the transport is ballistic. Based on the numerical analysis, we confirmed that our data can be explained in terms of the local Hall effect due to the profile of negative and positive field regions. This device may be useful for future spintronic applications.Comment: 4 pages with 4 fugures. Accepted for publication in Applied Physics Letter

Symplectic embedding and Hamilton-Jacobi analysis of Proca model

Following the symplectic approach we show how to embed the Abelian Proca model into a first-class system by extending the configuration space to include an additional pair of scalar fields, and compare it with the improved Dirac scheme. We obtain in this way the desired Wess-Zumino and gauge fixing terms of BRST invariant Lagrangian. Furthermore, the integrability properties of the second-class system described by the Abelian Proca model are investigated using the Hamilton-Jacobi formalism, where we construct the closed Lie algebra by introducing operators associated with the generalized Poisson brackets.Comment: 24 page

Proteolysis of Virulence Regulator Toxr is Associated with Entry of Vibrio Cholerae Into a Dormant State

Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP) in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL), and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC). Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state