Targets for the reduction of antibiotic use in humans in the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) partner countries.

Unnecessary and inappropriate use of antibiotics in human healthcare is a major driver for the development and spread of antimicrobial resistance; many countries are implementing measures to limit the overuse and misuse of antibiotics e.g. through the establishment of antimicrobial use reduction targets.

Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition.

The activity of Rho GTPases is carefully timed to control epithelial proliferation and differentiation. RhoA is downregulated when epithelial cells reach confluence, resulting in inhibition of signaling pathways that stimulate proliferation. Here we show that GEF-H1/Lfc, a guanine nucleotide exchange factor for RhoA, directly interacts with cingulin, a junctional adaptor.

Histone deacetylase inhibitors up-regulate the expression of tight junction proteins.

Histone deacetylase (HDAC) inhibitors promote cell maturation, differentiation, and apoptosis through changes in gene expression. Differentiated epithelial cells are characterized by apical tight junctions (TJ), which play a role in cell-cell adhesion, polarity, and the permeability barrier function of epithelia. The relationship between cellular differentiation and expression of TJ-associated proteins is not known.

Molecular complexity of vertebrate tight junctions (Review).

Separation of distinct body, organ and tissue compartments, and maintenance of epithelial cell polarity require tight junctions (TJ)-cell-cell junctions located in the apicolateral regions of epithelial and endothelial cells. Studies on the protein components of vertebrate TJ have revealed an intricate network of membrane, sub-membrane, cytoskeletal, and signalling molecules. How these molecules functionally interact to provide TJ with their functions, and what roles these molecules play in control of cell growth and differentiation is a fundamental problem in cell biology.

Evidence for a functional interaction between cingulin and ZO-1 in cultured cells.

Cingulin, a protein component of the submembrane plaque of tight junctions (TJ), contains globular and coiled-coil domains and interacts in vitro with several TJ and cytoskeletal proteins, including the PDZ protein ZO-1. Overexpression of Xenopus cingulin in transfected Xenopus A6 cells resulted in the disruption of endogenous ZO-1 localization, suggesting that cingulin functionally interacts with ZO-1. Glutathione S-transferase pull-down experiments showed that a conserved ZO-1 interaction motif (ZIM) at the NH(2) terminus of cingulin is required for cingulin-ZO-1 interaction in vitro.