Tipping the balance between and ligand conformers in multinuclear ethylzinc cyclophosphazenates.

Hexaanionic cyclophosphazenate ligands [(RN)PN] provide versatile platforms for the assembly of multinuclear metal arrays due to their multiple coordination sites and highly flexible ligand core structure. This work investigates the impact of incrementally increasing the steric demand of the ligand periphery on the coordination behavior of ethylzinc arrays. It shows that the increased congestion around the ligand sites is alleviated by progressive condensation with the elimination of diethylzinc.

Multiple cell types support productive infection and dynamic translocation of infectious Ebola virus to the surface of human skin.

Ebola virus (EBOV) causes severe human disease. During late infection, EBOV virions are on the skin's surface; however, the permissive skin cell types and the route of virus translocation to the epidermal surface are unknown. We describe a human skin explant model and demonstrate that EBOV infection of human skin via basal media increases in a time-dependent and dose-dependent manner.

Prioritising domains of glucocorticoid therapy to measure in trials: Results from a modified delphi exercise from the OMERACT glucocorticoid impact working group.

Introduction: There is no consensus amongst patients and healthcare professionals about how to measure important adverse effects of glucocorticoids (GCs) that includes the patient's perspective. The OMERACT GC Impact working group sought to identify the domains of greatest importance to both patients and healthcare professionals for use in a proposed core outcome set.

Methods: Patients and healthcare professionals participated in a Delphi consensus exercise to rate the importance of previously identified candidate domains.

Identification of TAK-756, A Potent TAK1 Inhibitor for the Treatment of Osteoarthritis through Intra-Articular Administration.

Osteoarthritis (OA) is a chronic and degenerative joint disease affecting more than 500 million patients worldwide with no disease-modifying treatment approved to date. Several publications report on the transforming growth factor β-activated kinase 1 (TAK1) as a potential molecular target for OA, with complementary anti-catabolic and anti-inflammatory effects. We report herein on the development of TAK1 inhibitors with physicochemical properties suitable for intra-articular injection, with the aim to achieve high drug concentration at the affected joint, while avoiding severe toxicity associated with systemic inhibition.