The base-catalyzed keto-enol tautomerism of chrysophanol anthrone. A DFT investigation of the base-catalyzed reaction

The keto-enol tautomerization of chrysophanol anthrone was systematically investigated via a series of density functional theory computations using the M06-2X/6-31?+?G(d,p) level of theory. Bulk solvent effects were taken into account implicitly using the polarisable continuum model and explicitly with one pyridine molecule. Moreover, the tautomeric equilibrium was estimated by calculating the equilibrium constant. The pyridine-assisted tautomerism was found to be the energetically preferred pathway, where the pyridine acts as a proton carrier through a two-step reaction, in which the first one corresponds to the deprotonation of the chrysophanol anthrone and the second step to the protonation yielding the enol form. The results show, in accordance with experimental reports, that in the process of dissociation of the protonated pyridine and the aryloxylate anion, the ion is quite susceptible to oxidation. The highly dipolar structures of the transition states and intermediates are stabilised by pyridine up to 7.0?kcal/mol. The non-covalent interactions stabilising the transition states and the intermediates were analysed. Additionally, an intermolecular hydrogen bonding between the enol form of chrysophanol anthrone and the pyridine is formed at the last stage of the reaction. The keto-enol equilibrium analysis shows that the enol form of chrysophanol anthrone must be present in small amounts in basic solvents.     

RGD cadherins and α2β1 integrin in cancer metastasis: A dangerous liaison

We propose a new cadherin family classification comprising epithelial cadherins (cadherin 17 [CDH17], cadherin 16, VE-cadherin, cadherin 6 and cadherin 20) containing RGD motifs within their sequences. Expression of some RGD cadherins is associated with aggressive forms of cancer during the late stages of metastasis, and CDH17 and VE-cadherin have emerged as critical actors in cancer metastasis. After binding to α2β1 integrin, these cadherins promote integrin β1 activation, and thereby cell adhesion, invasion and proliferation, in liver and lung metastasis. Activation of α2β1 integrin provokes an affinity increase for type IV collagen, a major component of the basement membrane and a critical partner for cell anchoring in liver and other metastatic organs. Activation of α2β1 integrin by RGD motifs breaks an old paradigm of integrin classification and supports an important role of this integrin in cancer metastasis. Recently, synthetic peptides containing the RGD motif of CDH17 elicited highly specific and selective antibodies that block the ability of CDH17 RGD to activate α2β1 integrin. These monoclonal antibodies inhibit metastatic colonization in orthotopic mouse models of liver and lung metastasis for colorectal cancer and melanoma, respectively. Hopefully, blocking the cadherin RGD ligand capacity will give us control over the integrin activity in solid tumors metastasis, paving the way for development of new agents of cancer treatment.     

The ontogeny of bone growth in two species of dormice: Reconstructing life history traits

Though bone histology has become a powerful tool to reconstruct life history strategies and physiology in living and extinct reptiles and amphibians, it is of limited use in mammals. Dormice (Myoxidae) are good candidates for assessing the relation between bone microstructure and life history due to their long life span, marked physiological cycles and negligible bone remodelling. We carried out the most comprehensive study so far analyzing 16 wild individuals of unknown age belonging to two different species of dormice, Glis glis and Eliomys quercinus. Our study shows a high degree of consistency in the number of resting lines present in bones of the same individual, with femora providing the most accurate age estimations. Moreover, the presence of a single LAG in some juveniles allows discerning between offspring from different reproductive events (early or late litters).