On the uniqueness of the non-minimal matter coupling in massive gravity and bigravity

In de Rham-Gabadadze-Tolley (dRGT) massive gravity and bigravity, a non-minimal matter coupling involving both metrics generically re-introduces the Boulware--Deser (BD) ghost. A non-minimal matter coupling via a simple, yet specific composite metric has been proposed, which eliminates the BD ghost below the strong coupling scale. Working explicitly in the metric formulation and for arbitrary spacetime dimensions, we show that this composite metric is the unique consistent non-minimal matter coupling below the strong coupling scale, which emerges out of two diagnostics, namely, absence of Ostrogradski ghosts in the decoupling limit and absence of the BD ghost from matter quantum loop corrections.Comment: v2: references added, matches accepted version in Physics Letters B v1: 6 pages, two-colum

Evaluation of Cardioprotective Effects of Genistein against Diabetes-induced Cardiac Dysfunction in Rats

Purpose: To investigate the possible cardioprotective effects and potential pharmacological mechanism of genistein.Methods: Six-week old ZDF and lean rats were randomized into 4 groups (8 rats/group), including group 1 (control lean rats); group 2 (lean rats treated with genistein, 2.5 mg/kg); group 3 (control ZDF rats); and group 4 (ZDF treated with genistein). Two groups (2 and 4) were treated with genistein for 12 weeks, and cardiac functions and metabolic alterations were determined. Macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription level also were observed.Results: Genistein attenuated diabetes-induced cardiac dysfunction and pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signalling pathways. In addition, genistein treatment markedly reduced diabetic-induced MCP-1 (83.33 %), VCAM-1 (74.66 %) and ICAM-1 (71.42 %) secretion and mRNA transcription in ZDF rats.Conclusion: The results demonstrate the putative effects of genistein against cardiovascular dysfunction by improving glucose homeostasis, attenuating oxidative stress and reduced diabeticinduced endothelial dysfunction in ZDF rats. Thus, genistein is a potential candidate for the prevention of cardiovascular diseases.Keywords: Cardiac dysfunction, Genistein, Oxidative stress, Inflammatory response, Insulin resistance, Glucose toleranc

Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase

<p>Abstract</p> <p>Background</p> <p>Activation of the RON receptor tyrosine kinase, a member of the c-MET family, regulates tumorigenic phenotypes. The RON extracellular domains are critical in regulating these activities. The objective of this study was to determine the role of the first IPT domain in regulating RON-mediated tumorigenic activities and the underlying mechanisms.</p> <p>Results</p> <p>Two RON variants, RON160 and RON^E5/6inwith deletion and insertion in the first IPT domain, respectively, were molecularly cloned. RON160 was a splicing variant generated by deletion of 109 amino acids encoded by exons 5 and 6. In contrast, RON^E5/6inwas derived from a transcript with an insertion of 20 amino acids between exons 5 and 6. Both RON160 and RON^E5/6inwere proteolytically matured into two-chain receptor and expressed on the cell surface. RON160 was constitutively active with tyrosine phosphorylation. However, activation of RON^E5/6inrequired ligand stimulation. Deletion resulted in the resistance of RON160 to proteolytic digestion by cell associated trypsin-like enzymes. RON160 also resisted anti-RON antibody-induced receptor internalization. These features contributed to sustained intracellular signaling cascades. On the other hand, RON^E5/6inwas highly susceptible to protease digestion, which led to formation of a truncated variant known as RONp110. RON^E5/6inalso underwent rapid internalization upon anti-RON antibody treatment, which led to signaling attenuation. Although ligand-induced activation of RON^E5/6inpartially caused epithelial to mesenchymal transition (EMT), it was RON160 that showed cell-transforming activities in cell focus formation and anchorage-independent growth. RON160-mediated EMT is also associated with increased motile/invasive activity.</p> <p>Conclusions</p> <p>Alterations in the first IPT domain in extracellular region differentially regulate RON mediated tumorigenic activities. Deletion of the first IPT results in formation of oncogenic variant RON160. Enhanced degradation and internalization with attenuated signaling cascades could be the mechanisms underlying non-tumorigenic features of RON^E5/6in.</p