Rabbit Anti-Human AR Monoclonal Antibody, clone CQ7237

Boosting energy expenditure by harnessing the activity of brown adipocytes is a promising strategy for combatting the global epidemic of obesity. Many studies have revealed that the beta(3)-adrenergic receptor agonist is a potent activator of brown adipocytes, even in humans, and PKA and p38 MAPK have been demonstrated for regulating the transcription of a wide range of critical genes such as Ucp1. We previously revealed that the PKA-ASK1-p38 axis is activated in immature brown adipocytes and contributes to functional maturation. However, the downstream mechanisms of PKA that initiate the p38 MAPK cascade are still mostly unknown in mature brown adipocytes. Here, we identified the ASK family as a crucial signaling molecule bridging PKA and MAPK in mature brown adipocytes. Mechanistically, the phosphorylation of ASK1 at threonine 99 and serine 993 is critical in PKA-dependent ASK1 activation. Additionally, PKA also activates ASK2, which contributes to MAPK regulation. These lines of evidence provide new details for tailoring a beta AR-dependent brown adipocyte activation strategy.

Argon gas cluster ion beams (Ar-GCIBs) provide new opportunities for molecular depth profiling and imaging of organic materials and biological samples, thanks to recent technological developments that have led to the construction of new SIMS spectrometers where the traditional issues related to their low lateral resolution along with poor mass resolution and mass accuracy are overcome. The present fundamental contribution on SIMS molecular depth profiling investigates the variations of the secondary ion signals observed at the organic-inorganic hybrid interface when using Ar-GCIB as the analytical beam. With this in mind, depth profiling experiments were performed with a ToF-SIMS spectrometer using different analysis beams: 30-keV Bi-5(+) versus 10-keV Ar-n(+) with a cluster size (n) of 800, 1500, 3000 and 5000 atoms, respectively. A 10-keV Ar-3000+ beam was used for sputtering in all the experiments. Irganox 1010 and model polymers such as polystyrene (PS) and poly (methyl methacrylate) (PMMA) oligomers were chosen. Silicon wafer and a polymer-based substrates were employed to test materials with different stiffness, which is directly related to their Young's moduli, an important parameter in this study. ArGCIB depth profiles systematically show ion signal enhancement of the characteristic fragments of PS and Irganox 1010 when approaching the interface with the silicon substrate, that can reach up to 60% for [M1010-H]- in Irganox films deposited onto silicon wafers. This enhancement increases with increasing n in both ion polarities. These results point out some ionization effects on the observed signal enhancement at the interface. The experimental observations will be explained on the basis of the physics of the impact of large argon clusters on different target materials and the energy confinement of the ion projectile in the organic overlayers. Finally, the thickness of organic films on rigid substrates in the nanoscale appears to be a crucial parameter to dramatically improve the sensitivity to molecular fragments when using large Ar cluster ions as analysis beams.