Controlling receptor-mediated processes in cells is paramount in many research areas. The activity of small molecules and growth factors is difficult to control and can lead to off-target effects through the activation of nonspecific receptors as well as binding affinity to nonspecific cell types. In this study, we report the development of a molecular trigger in the form of a divalent nucleic acid aptamer assembly toward vascular endothelial growth factor receptor-2 (VEGFR2). The assembly binds to VEGFR2 and functions as a receptor agonist with targeted receptor binding, promoting receptor phosphorylation, activation of the downstream Akt pathway, upregulation of endothelial nitric oxide synthase, and endothelial cell capillary tube formation. The agonist action we report makes this aptamer construct a promising strategy to control VEGFR2-mediated cell signaling.

No abstract

Magnesium-based alloys have attracted interest as a potential material to comprise biomedical implants that are simultaneously high-strength and temporary, able to provide stabilization before degrading safely and able to be excreted by the human body. Many alloy systems have been evaluated, but this work reports on improved properties through hot extrusion of one promising alloy: Mg-1.0 wt% Ca-0.5 wt%Sr. This alloy has previously demonstrated promising toxicity and degradation properties in the as-cast and rolled conditions. In the current study extrusion causes a dramatic improvement in the mechanical properties in tension and compression, as well as a low in vitro degradation rate. Microstructure (texture, second phase distribution, and grain size), bulk mechanical properties, flow behavior, degradation in simulated body fluid, and effect on osteoblast cyctotoxicity are evaluated and correlated to extrusion temperature. Maximum yield strength of 300 MPa (above that of annealed 316 stainless steel) with 10% elongation is observed, making this alloy competitive with existing implant materials.

Satellite observations show a near-zero trend in the top-of-atmosphere global-mean net cloud radiative effect (CRE), suggesting that clouds did not further cool nor heat the planet over the last two decades. The causes of this observed trend are unknown and can range from effective radiative forcing (ERF), cloud feedbacks, cloud masking, to internal variability. We find that the near-zero NetCRE trend is a result of a significant negative trend in the longwave (LW) CRE and a significant positive trend in the shortwave (SW) CRE, cooling and heating the climate system, respectively. We find that it is exceptionally unlikely (<1% probability) that internal variability can explain the observed LW and SW CRE trends. Instead, the majority of the observed LWCRE trend arises from cloud masking wherein increases in greenhouse gases reduce OLR in all-sky conditions less than in clear-sky conditions. In SWCRE, rapid cloud adjustments to greenhouse gases, aerosols, and natural forcing agents (ERF) explain a majority of the observed trend. Over the Northeast Pacific, we show that ERF, hitherto an ignored factor, contributes as much as cloud feedbacks to the observed SWCRE trend. Large contributions from ERF and cloud masking to the global-mean LW and SW CRE trends are supplemented by negative LW and positive SW cloud feedback trends, which are detectable at 80-95% confidence depending on the observational uncertainty assumed. The large globalmean LW and SW cloud feedbacks cancel, leaving a small net cloud feedback that is unconstrained in sign, implying that clouds could amplify or dampen global warming.