Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII

Regulation of intracellular cyclic adenosine 3’, 5’-monophosphate (cAMP) by multiple pathways enables differential function of this ubiquitous second messenger in a context dependent manner. Modulation of Gs-stimulated intracellular cAMP has long been known to be modulated by the Gi and Gq/Ca2+ pathways. Recently, the G13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the Gs and G13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the alpha subunit of either G12 or G13. Our results demonstrate that AC7 is a specific downstream effector of the G12/13 pathway

A second order algebraic knot concordance group

We define an algebraic group comprising symmetric chain complexes which captures the first two stages of the Cochran-Orr-Teichner solvable filtration of the knot concordance group in a single invariant. To achieve this we impose additional structure on each chain complex which puts extra control on the fundamental groups, and in particular on the way in which they can change in a concordance.Comment: 51 pages, 2 figures. This a considerably shortened version of arXiv:1109.0761, to appear in Algebraic and Geometric Topolog

Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

PMCID: PMC3212807This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

A minimal nonfinitely based semigroup whose variety is polynomially recognizable

We exhibit a 6-element semigroup that has no finite identity basis but nevertheless generates a variety whose finite membership problem admits a polynomial algorithm.Comment: 16 pages, 3 figure