Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching

Vitamin D receptor (VDR) is essential for ligand-induced gene repression of 25(OH)D(3) 1α-hydroxylase (1α(OH)ase) in mammalian kidney, while this gene expression is activated by protein kinase A (PKA) signaling downstream of the parathyroid hormone action. The mapped negative vitamin D response element (1αnVDRE) in the human 1α(OH)ase gene promoter (around 530 bp) was distinct from those of the reported DR3-like nVDREs, composed of two E-box-like motifs. Unlike the reported nVDREs, no direct binding of VDR/RXR heterodimer to 1αnVDRE was detected. A bHLH-type factor, designated VDIR, was identified as a direct sequence-specific activator of 1αnVDRE. The transactivation function of VDIR was further potentiated by activated-PKA signaling through phosphorylation of serine residues in the transactivation domains, with the recruitment of a p300 histone acetyltransferase co-activator. The ligand-dependent association of VDR/RXR heterodimer with VDIR bound to 1αnVDRE caused the dissociation of p300 co-activators from VDIR, and the association of HDAC co-repressor complex components resulting in ligand-induced transrepression. Thus, the present study deciphers a novel mechanism of ligand-induced transrepression by nuclear receptor via co-regulator switching

Steam recovery from flue gas by organosilica membranes for simultaneous harvesting of water and energy

Abstract Steam recovery from the spent gases from flues could be a key step in addressing the water shortage issue while additionally benefiting energy saving. Herein, we propose a system that uses organosilica membranes consisting of a developed layered structure to recover steam and latent heat from waste. Proof-of-concept testing is conducted in a running incinerator plant. The proposed system eliminates the need for a water supply while simultaneously recovering latent heat from the waste stream. First, the long-term stability of an organosilica membrane is confirmed over the course of six months on a laboratory-scale under a simulated waste stream. Second, steam recovery is demonstrated in a running waste incinerator plant (bench-scale), which confirms the steady operation of this steam recovery system with a steam recovery rate comparable to that recorded in the laboratory-scale test. Third, process simulation reveals that this system enables water-self-reliance with energy recovery that approximates 70% of waste combustion energy

The Crosstalk between Osteoclasts and Osteoblasts Is Dependent upon the Composition and Structure of Biphasic Calcium Phosphates

Biphasic calcium phosphates (BCPs), consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), exhibit good biocompatibility and osteoconductivity, maintaining a balance between resorption of the biomaterial and formation of new bone. We tested whether the chemical composition and/or the microstructure of BCPs affect osteoclasts (OCs) differentiation and/or their ability to crosstalk with osteoblasts (OBs). To this aim, OCs were cultured on BCPs with HA content of 5, 20 or 60% and their differentiation and activity were assessed. We found that OC differentiation is partially impaired by increased HA content, but not by the presence of micropores within BCP scaffolds, as indicated by TRAP staining and gene profile expression. We then investigated whether the biomaterial-induced changes in OC differentiation also affect their ability to crosstalk with OBs and regulate OB function. We found that BCPs with low percentage of HA favored the expression of positive coupling factors, including sphingosine-kinase 1 (SPHK1) and collagen triple helix repeat containing 1 (Cthrc1). In turn, the increase of these secreted coupling factors promotes OB differentiation and function. All together our studies suggest that the chemical composition of biomaterials affects not only the differentiation and activity of OCs but also their potential to locally regulate bone formation