Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following Spinal Cord Injury.

Impact statementSpinal cord injury (SCI) results in loss of tissue innervation below the injury. Spinal progenitors have a greater ability to repair the damage and can be injected into the injury, but their regenerative potential is hampered by their poor survival after transplantation. Biomaterials can create a cell delivery platform and generate a more hospitable microenvironment for the progenitors within the injury. In this work, polymeric bridges are used to deliver embryonic spinal progenitors to the injury, resulting in increased progenitor survival and subsequent regeneration and functional recovery, thus demonstrating the importance of combined therapeutic approaches for SCI

Polycistronic Delivery of IL-10 and NT-3 Promotes Oligodendrocyte Myelination and Functional Recovery in a Mouse Spinal Cord Injury Model.

One million estimated cases of spinal cord injury (SCI) have been reported in the United States and repairing an injury has constituted a difficult clinical challenge. The complex, dynamic, inhibitory microenvironment postinjury, which is characterized by proinflammatory signaling from invading leukocytes and lack of sufficient factors that promote axonal survival and elongation, limits regeneration. Herein, we investigated the delivery of polycistronic vectors, which have the potential to coexpress factors that target distinct barriers to regeneration, from a multiple channel poly(lactide-co-glycolide) (PLG) bridge to enhance spinal cord regeneration. In this study, we investigated polycistronic delivery of IL-10 that targets proinflammatory signaling, and NT-3 that targets axonal survival and elongation. A significant increase was observed in the density of regenerative macrophages for IL-10+NT-3 condition relative to conditions without IL-10. Furthermore, combined delivery of IL-10+NT-3 produced a significant increase of axonal density and notably myelinated axons compared with all other conditions. A significant increase in functional recovery was observed for IL-10+NT-3 delivery at 12 weeks postinjury that was positively correlated to oligodendrocyte myelinated axon density, suggesting oligodendrocyte-mediated myelination as an important target to improve functional recovery. These results further support the use of multiple channel PLG bridges as a growth supportive substrate and platform to deliver bioactive agents to modulate the SCI microenvironment and promote regeneration and functional recovery. Impact statement Spinal cord injury (SCI) results in a complex microenvironment that contains multiple barriers to regeneration and functional recovery. Multiple factors are necessary to address these barriers to regeneration, and polycistronic lentiviral gene therapy represents a strategy to locally express multiple factors simultaneously. A bicistronic vector encoding IL-10 and NT-3 was delivered from a poly(lactide-co-glycolide) bridge, which provides structural support that guides regeneration, resulting in increased axonal growth, myelination, and subsequent functional recovery. These results demonstrate the opportunity of targeting multiple barriers to SCI regeneration for additive effects

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination.

Spinal cord injury (SCI) is a devastating condition that may cause permanent functional loss below the level of injury, including paralysis and loss of bladder, bowel, and sexual function. Patients are rarely treated immediately, and this delay is associated with tissue loss and scar formation that can make regeneration at chronic time points more challenging. Herein, we investigated regeneration using a poly(lactide-co-glycolide) multichannel bridge implanted into a chronic SCI following surgical resection of necrotic tissue. We characterized the dynamic injury response and noted that scar formation decreased at 4 and 8 weeks postinjury (wpi), yet macrophage infiltration increased between 4 and 8 wpi. Subsequently, the scar tissue was resected and bridges were implanted at 4 and 8 wpi. We observed robust axon growth into the bridge and remyelination at 6 months after initial injury. Axon densities were increased for 8 week bridge implantation relative to 4 week bridge implantation, whereas greater myelination, particularly by Schwann cells, was observed with 4 week bridge implantation. The process of bridge implantation did not significantly decrease the postinjury function. Collectively, this chronic model follows the pathophysiology of human SCI, and bridge implantation allows for clear demarcation of the regenerated tissue. These data demonstrate that bridge implantation into chronic SCI supports regeneration and provides a platform to investigate strategies to buttress and expand regeneration of neural tissue at chronic time points

Influence of s,p-d and s-p exchange couplings on exciton splitting in (Zn,Mn)O

This work presents results of near-band gap magnetooptical studies on (Zn,Mn)O epitaxial layers. We observe excitonic transitions in reflectivity and photoluminescence, that shift towards higher energies when the Mn concentration increases and split nonlinearly under the magnetic field. Excitonic shifts are determined by the s,p-d exchange coupling to magnetic ions, by the electron-hole s-p exchange, and the spin-orbit interactions. A quantitative description of the magnetoreflectivity findings indicates that the free excitons A and B are associated with the Gamma_7 and Gamma_9 valence bands, respectively, the order reversed as compared to wurtzite GaN. Furthermore, our results show that the magnitude of the giant exciton splittings, specific to dilute magnetic semiconductors, is unusual: the magnetoreflectivity data is described by an effective exchange energy N_0(beta-alpha)=+0.2+/-0.1 eV, what points to small and positive N_0 beta. It is shown that both the increase of the gap with x and the small positive value of the exchange energy N_0 beta corroborate recent theory describing the exchange splitting of the valence band in a non-perturbative way, suitable for the case of a strong p-d hybridization.Comment: 8 pages, 8 figure

Modeling the Biomass Production of Grasslands of Wallonia According to their Functional Type

Permanent grasslands are complex ecosystems which respond with a great variability - in terms of specific richness - to soil type and management strategies. Modelling is a valuable tool to explore these relationships. Our work consisted in adapting the Moorepark St Gilles grass growth model (MoSt GG) designed to model Lolium perenne plant functional type (PFT) pastures (PFT A) to a different PFT (Dactylis glomerata, PFT B) through literature-based parametrization. The model was evaluated under Walloon (Belgium) conditions using growth trials from 2014 to 2018 in two sites with contrasting pedo-climatic conditions. Three to five cuts were performed over the course of the growing seasons depending on the rainfall yielding a total of 20 and 25 biomass measurements (kg of DM per ha), for PFT A and B respectively. No site effects were observed in the performance of the model. The relative root mean square error (RRMSE), normalized deviation (ND) and model efficiency (EF) across all cuts, sites and PFTs were 33%, 3% and 68% respectively. PFT B was better simulated than A for the criteria RRMSE (33% vs 33%), ND (4% vs. 9%), and EF (75% vs. 54%). Although this first evaluation was satisfactory, a complementary parametrization for additional pedoclimatic conditions and PFTs is called for to use the model under the diversity of Walloon condition

The Origin of Fe II Emission in AGN

We used a very large set of models of broad emission line (BEL) clouds in AGN to investigate the formation of the observed Fe II emission lines. We show that photoionized BEL clouds cannot produce both the observed shape and observed equivalent width of the 2200-2800A Fe II UV bump unless there is considerable velocity structure corresponding to a microturbulent velocity parameter v_turb > 100 km/s for the LOC models used here. This could be either microturbulence in gas that is confined by some phenomenon such as MHD waves, or a velocity shear such as in the various models of winds flowing off the surfaces of accretion disks. The alternative way that we can find to simultaneously match both the observed shape and equivalent width of the Fe II UV bump is for the Fe II emission to be the result of collisional excitation in a warm, dense gas. Such gas would emit very few lines other than Fe II. However, since the collisionally excited gas would constitute yet another component in an already complicated picture of the BELR, we prefer the model involving turbulence. In either model, the strength of Fe II emission relative to the emission lines of other ions such as Mg II depends as much on other parameters (either v_turb or the surface area of the collisionally excited gas) as it does on the iron abundance. Therefore, the measurement of the iron abundance from the FeII emission in quasars becomes a more difficult problem.Comment: 23 pages. Accepted by Ap