Inhibition of the H1 voltage-gated proton channel compromises the viability of human polarized macrophages in a polarization- and ceramide-dependent manner.

The human voltage-gated proton channel (H1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit H1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2-guanidinobenzimidazole (ClGBI), the most widely applied H1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound.

Particularities of deposition of two ICS-LABA fixed dose combination dry powder aerosol drugs in the airways of COPD patients.

The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS + LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85 % of the patients.

Magnetic structures in the explicitly time-dependent nontwist map.

We investigate how the magnetic structures of the plasma change in a large aspect ratio tokamak perturbed by an ergodic magnetic limiter, when a system parameter is non-adiabatically varied in time. We model such a scenario by considering the Ullmann-Caldas nontwist map, where we introduce an explicit time-dependence to the ratio of the limiter and plasma currents. We apply the tools developed recently in the field of chaotic Hamiltonian systems subjected to parameter drift.

Genomics identifies koala populations at risk across eastern Australia.

Koalas are an iconic, endangered, Australian marsupial. Disease, habitat destruction, and catastrophic mega-fires have reduced koalas to remnant patches of their former range. With increased likelihood of extreme weather events and ongoing habitat clearing across Australia, koala populations are vulnerable to further declines and isolation.