Thermostable Direct Hemolysin Downregulates Human Colon Carcinoma Cell Proliferation with the Involvement of E-Cadherin, and β-Catenin/Tcf-4 Signaling

BACKGROUND: Colon cancers are the frequent causes of cancer mortality worldwide. Recently bacterial toxins have received marked attention as promising approaches in the treatment of colon cancer. Thermostable direct hemolysin (TDH) secreted by Vibrio parahaemolyticus causes influx of extracellular calcium with the subsequent rise in intracellular calcium level in intestinal epithelial cells and it is known that calcium has antiproliferative activity against colon cancer. KEY RESULTS: In the present study it has been shown that TDH, a well-known traditional virulent factor inhibits proliferation of human colon carcinoma cells through the involvement of CaSR in its mechanism. TDH treatment does not induce DNA fragmentation, nor causes the release of lactate dehydrogenase. Therefore, apoptosis and cytotoxicity are not contributing to the TDH-mediated reduction of proliferation rate, and hence the reduction appears to be caused by decrease in cell proliferation. The elevation of E-cadherin, a cell adhesion molecule and suppression of β-catenin, a proto-oncogene have been observed in presence of CaSR agonists whereas reverse effect has been seen in presence of CaSR antagonist as well as si-RNA in TDH treated cells. TDH also triggers a significant reduction of Cyclin-D and cdk2, two important cell cycle regulatory proteins along with an up regulation of cell cycle inhibitory protein p27(Kip1) in presence of CaSR agonists. CONCLUSION: Therefore TDH can downregulate colonic carcinoma cell proliferation and involves CaSR in its mechanism of action. The downregulation occurs mainly through the involvement of E-cadherin-β-catenin mediated pathway and the inhibition of cell cycle regulators as well as upregulation of cell cycle inhibitors

Bayesian Fit of Exclusive b→sℓˉℓb \to s \bar\ell\ell Decays: The Standard Model Operator Basis

We perform a model-independent fit of the short-distance couplings $C_{7,9,10}$ within the Standard Model set of $b\to s\gamma$ and $b\to s\bar\ell\ell$ operators. Our analysis of $B \to K^* \gamma$, $B \to K^{(*)} \bar\ell\ell$ and $B_s \to \bar\mu\mu$ decays is the first to harness the full power of the Bayesian approach: all major sources of theory uncertainty explicitly enter as nuisance parameters. Exploiting the latest measurements, the fit reveals a flipped-sign solution in addition to a Standard-Model-like solution for the couplings $C_i$. Each solution contains about half of the posterior probability, and both have nearly equal goodness of fit. The Standard Model prediction is close to the best-fit point. No New Physics contributions are necessary to describe the current data. Benefitting from the improved posterior knowledge of the nuisance parameters, we predict ranges for currently unmeasured, optimized observables in the angular distributions of $B\to K^*(\to K\pi)\,\bar\ell\ell$.Comment: 42 pages, 8 figures; v2: Using new lattice input for f_Bs, considering Bs-mixing effects in BR[B_s->ll]. Main results and conclusion unchanged, matches journal versio

Electroweak Baryogenesis in Two Higgs Doublet Models and B meson anomalies

Motivated by 3.9 sigma evidence of a CP-violating phase beyond the standard model in the like-sign dimuon asymmetry reported by DO, we examine the potential for two Higgs doublet models (2HDMs) to achieve successful electroweak baryogenesis (EWBG) while explaining the dimuon anomaly. Our emphasis is on the minimal flavour violating 2HDM, but our numerical scans of model parameter space include type I and type II models as special cases. We incorporate relevant particle physics constraints, including electroweak precision data, b to s gamma, the neutron electric dipole moment, R_b, and perturbative coupling bounds to constrain the model. Surprisingly, we find that a large enough baryon asymmetry is only consistently achieved in a small subset of parameter space in 2HDMs, regardless of trying to simultaneously account for any B physics anomaly. There is some tension between simultaneous explanation of the dimuon anomaly and baryogenesis, but using a Markov chain Monte Carlo we find several models within 1 sigma of the central values. We point out shortcomings with previous studies that reached different conclusions. The restricted parameter space that allows for EWBG makes this scenario highly predictive for collider searches. We discuss the most promising signatures to pursue at the LHC for EWBG-compatible models.Comment: 58 pages, 16 figures, 6 tables; v2 added references; v3 minor corrections and improvements, published versio

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe