B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems

Contrasting variations of ecosystem gross primary productivity during flash droughts caused by competing water demand and supply

Flash drought events (FDEs) are projected to increase frequently in a warming world, significantly impacting ecosystem productivity and the global carbon cycle. The development of FDEs, induced by anomalies in different environmental variables, may cause different responses to the ecosystem’s gross primary productivity (GPP). However, the GPP variations and underlying mechanisms during the FDEs have rarely been quantified. This study collected long-term (>10 years) high-quality flux observations from the FLUXNET 2015 dataset to investigate GPP variations and their driving mechanisms during FDEs. Results showed that all vegetation types have two contrasting GPP variations during FDEs. One variation is a decreasing then increasing standardized GPP anomaly (V-shape response). The other shows an increase followed by decreasing standardized GPP anomaly (inverted V-shape response). The V-shape GPP response to FDEs was induced by increased soil water content deficit at the onset stage of FDEs. In contrast, the inverted V-shape GPP response to FDEs was induced by increased net radiation at the onset of FDEs. Such results indicated competing moisture supply and atmospheric moisture demand at the onset of FDEs, controlling the two contrasting ecosystem’s carbon responses with its development. Moreover, the contribution of water use efficiency to the magnitude of the V-shape GPP response (64.5 ± 22.4%) is greater than that to the inverted V-shape GPP response (47.6 ± 18.7%). This study identified the two contrasting types of GPP variations during FDEs and their driving mechanisms across multiple ecosystem types which can improve our ability to predict the future effects of more frequent FDEs on ecosystem productivity

Land surface models significantly underestimate the impact of land-use changes on global evapotranspiration

Despite numerous assessments of the impact of land-use change (LUC) on terrestrial evapotranspiration (ET) that have been conducted using land surface models (LSMs), no attempts have been made to evaluate their performance in this regard globally. Errors in simulating LUC impacts on ET largely stem from LUC data interpretation (LI, i.e. mapping of gridded LUC data into annual plant function types) and model structure (MS, i.e. parameterization of land-surface processes). The objective of this study was to benchmark ET estimates from four LSMs using the Zhang-curve, a prototype of the Budyko framework that has been validated against global hydrological observations and used widely to quantify the impacts of LUC on ET. A framework was further proposed to quantify and attribute errors in estimated ET changes induced by LI or MS. Results showed that all LSMs underestimated ET changes by about 55%–78%, and 37%–48% of the error was attributable to LI, but only 11%–32% of the error was attributable to MS across the four LSMs. From a hydrological perspective, our analysis provided insights about the errors in estimated impacts of LUC on ET by LSMs. The results demonstrated that LUC data interpretation accounted for a larger fraction of errors than LSM structure. Therefore, there is an urgent need for the defining and development of consistent protocols for interpreting global LUC data for future assessments

Remote Manipulation of Ligand Nano-Oscillations Regulates Adhesion and Polarization of Macrophages in Vivo

Macrophages play crucial roles in various immune-related responses, such as host defense, wound healing, disease progression, and tissue regeneration. Macrophages perform distinct and dynamic functions in vivo, depending on their polarization states, such as the pro-inflammatory M1 phenotype and pro-healing M2 phenotype. Remote manipulation of the adhesion of host macrophages to the implants and their subsequent polarization in vivo can be an attractive strategy to control macrophage polarization-specific functions but has rarely been achieved. In this study, we grafted RGD ligand-bearing superparamagnetic iron oxide nanoparticles (SPIONs) to a planar matrix via a long flexible linker. We characterized the nanoscale motion of the RGD-bearing SPIONs grafted to the matrix, in real time by in situ magnetic scanning transmission electron microscopy (STEM) and in situ atomic force microscopy. The magnetic field was applied at various oscillation frequencies to manipulate the frequency-dependent ligand nano-oscillation speeds of the RGD-bearing SPIONs. We demonstrate that a low oscillation frequency of the magnetic field stimulated the adhesion and M2 polarization of macrophages, whereas a high oscillation frequency suppressed the adhesion of macrophages but promoted their M1 polarization, both in vitro and in vivo. Macrophage adhesion was also temporally regulated by switching between the low and high frequencies of the oscillating magnetic field. To the best of our knowledge, this is the first demonstration of the remote manipulation of the adhesion and polarization phenotype of macrophages, both in vitro and in vivo. Our system offers the promising potential to manipulate host immune responses to implanted biomaterials, including inflammation or tissue reparative processes, by regulating macrophage adhesion and polarization