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Cell migration is essential to embryonic development, wound healing, and cancer cell dissemination. Cells move via leading-edge protrusion, substrate adhesion, and retraction of the cell's rear. The molecular mechanisms by which extracellular cues signal to the actomyosin cytoskeleton to control these motility mechanics are poorly understood. The growth factor-responsive and oncogenically activated protein extracellular signal-regulated kinase (ERK) promotes motility by signaling in actin polymerization-mediated edge protrusion. Using a combination of immunoblotting, co-immunoprecipitation, and myosin-binding experiments and cell migration assays, we show here that ERK also signals to the contractile machinery through its substrate, p90 ribosomal S6 kinase (RSK). We probed the signaling and migration dynamics of multiple mammalian cell lines and found that RSK phosphorylates myosin phosphatase-targeting subunit 1 (MYPT1) at Ser-507, which promotes an interaction of Rho kinase (ROCK) with MYPT1 and inhibits myosin targeting. We find that by inhibiting the myosin phosphatase, ERK and RSK promote myosin II-mediated tension for lamella expansion and optimal edge dynamics for cell migration. These findings suggest that ERK activity can coordinately amplify both protrusive and contractile forces for optimal cell motility., (© 2019 Samson et al.)

The eukaryotic cell's microtubule cytoskeleton is a complex 3D filament network. Microtubules cross at a wide variety of separation distances and angles. Prior studies in vivo and in vitro suggest that cargo transport is affected by intersection geometry. However, geometric complexity is not yet widely appreciated as a regulatory factor in its own right, and mechanisms that underlie this mode of regulation are not well understood. We have used our recently reported 3D microtubule manipulation system to build filament crossings de novo in a purified in vitro environment and used them to assay kinesin-1-driven model cargo navigation. We found that 3D microtubule network geometry indeed significantly influences cargo routing, and in particular that it is possible to bias a cargo to pass or switch just by changing either filament spacing or angle. Furthermore, we captured our experimental results in a model which accounts for full 3D geometry, stochastic motion of the cargo and associated motors, as well as motor force production and force-dependent behavior. We used a combination of experimental and theoretical analysis to establish the detailed mechanisms underlying cargo navigation at microtubule crossings., Competing Interests: Conflict of interest statement: M.V.G. is employed by Bruker Nano Surfaces. The authors declare no conflict of interest.

The optical signatures of Mg-related acceptors in GaN have been revisited in samples specifically grown on bulk GaN templates, to avoid strain broadening of the optical spectra. Bound-exciton spectra can be studied in these samples for Mg concentrations up to [Mg] approximately 2 x 10(19) cm(-3). Contrary to previous work it is found that instabilities in the photoluminescence spectra are not due to unstable shallow donors, but to unstable Mg-related acceptors. Our data show that there are two Mg-related acceptors simultaneously present: the regular (stable) substitutional Mg acceptor, and a complex acceptor which is unstable in p-GaN.

We report on a strong delay in light propagation through bulk GaN, detected by time-of-flight spectroscopy. The delay increases resonantly as the photon energy approaches the energy of a neutral-donor bound exciton (BX), resulting in a velocity of light as low as 2100 km/s. In the close vicinity of the BX resonance, the transmitted light contains both ballistic and diffusive components. This phenomenon is quantitatively explained in terms of optical dispersion in a medium where resonant light scattering by the BX resonance takes place in addition to the polariton propagation.

A novel series of 5-aryl thiazolidine-2,4-diones based dual PPARalpha/gamma agonists was identified. A number of highly potent and orally bioavailable analogues were synthesized. Efficacy study results of some of these analogues in the db/db mice model of type 2 diabetes showed them superior to rosiglitazone in correcting hyperglycemia and hypertriglyceridemia.

A series of 5-aryl thiazolidine-2,4-diones containing 4-phenoxyphenyl side chains was designed, synthesized, and evaluated for PPAR agonist activities. One such compound 28 exhibited comparable levels of glucose correction to rosiglitazone in the db/db mouse type 2 diabetes animal model.