After a spinal cord injury, axons fail to regenerate in the adult mammalian central nervous system, leading to permanent deficits in sensory and motor functions. Increasing neuronal activity after an injury using electrical stimulation or rehabilitation can enhance neuronal plasticity and result in some degree of recovery; however, the underlying mechanisms remain poorly understood. We found that placing mice in an enriched environment before an injury enhanced the activity of proprioceptive dorsal root ganglion neurons, leading to a lasting increase in their regenerative potential. This effect was dependent on Creb-binding protein (Cbp)–mediated histone acetylation, which increased the expression of genes associated with the regenerative program. Intraperitoneal delivery of a small-molecule activator of Cbp at clinically relevant times promoted regeneration and sprouting of sensory and motor axons, as well as recovery of sensory and motor functions in both the mouse and rat model of spinal cord injury. Our findings showed that the increased regenerative capacity induced by enhancing neuronal activity is mediated by epigenetic reprogramming in rodent models of spinal cord injury. Understanding the mechanisms underlying activity-dependent neuronal plasticity led to the identification of potential molecular targets for improving recovery after spinal cord injury.
Chromatin acetylation, a critical regulator of synaptic plasticity and memory processes, is thought to be altered in neurodegenerative diseases. Here, we demonstrate that spatial memory and plasticity (LTD, dendritic spine formation) deficits can be restored in a mouse model of tauopathy following treatment with CSP‐TTK21, a small‐molecule activator of CBP/p300 histone acetyltransferases (HAT). At the transcriptional level, CSP‐TTK21 re‐established half of the hippocampal transcriptome in learning mice, likely through increased expression of neuronal activity genes and memory enhancers. At the epigenomic level, the hippocampus of tauopathic mice showed a significant decrease in H2B but not H3K27 acetylation levels, both marks co‐localizing at TSS and CBP enhancers. Importantly, CSP‐TTK21 treatment increased H2B acetylation levels at decreased peaks, CBP enhancers, and TSS, including genes associated with plasticity and neuronal functions, overall providing a 95% rescue of the H2B acetylome in tauopathic mice. This study is the first to provide in vivo proof‐of‐concept evidence that CBP/p300 HAT activation efficiently reverses epigenetic, transcriptional, synaptic plasticity, and behavioral deficits associated with Alzheimer's disease lesions in mice.
Developing environment-friendly active and selective catalysts for oxidative dehydrogenation of propane for on-purpose propene synthesis is challenging despite tremendous industrial potential for this reaction. Herein, we report on catalytic activity of high surface area hexagonal boron nitride, toward oxidative dehydrogenation of propane. It shows remarkable selectivity for alkenes (∼70%) at very high conversion (of ∼50%) of propane. Propene and ethene selectivities as high as 53 and 18%, respectively, were obtained at a conversion of 52%. The catalytic activity is retained continuously for 5 h. Regeneration in ammonia brings back the catalytic activity to its full potential. Oxidation of surface B–N bonds in oxygen leads to the diminishing catalytic activity after 5 h which, on heating in ammonia, reduced back to their native form, regaining the indigenous activity. Remarkably, the addition of ammonia in the reaction feed showed stable activity for more than 100 h.
The surface areas and uptake of CO(2) and CH(4) by four graphene samples are measured and compared with activated charcoal. The surface areas are in the range of 5-640 m(2) g(-1), whereas the CO(2) and CH(4) uptake values are in the range of 18-45 wt % (at 195 K, 0.1 MPa) and 0-2.8 wt % (at 273 K, 5 MPa), respectively. The CO(2) and CH(4) uptake values of the graphene samples vary linearly with the surface area. In contrast, graphene-like B(x)C(y)N(z) samples with compositions close to BC(2)N exhibit surface areas in the range of 1500-1990 m(2) g(-1) and CO(2) and CH(4) uptake values in the ranges 97-128 wt % (at 195 K, 0.1 MPa) and 7.5-17.3 wt %, respectively. The uptake of these gases varies exponentially with the surface area of the B(x)C(y)Z(n) samples, and the uptake of CH(4) varies proportionally with that of CO(2). The uptake of CO(2) for the best BC(2)N sample is 64 wt % at 298 K. The large uptake of both CO(2) and CH(4) gases by BC(2)N betters the performance of graphenes and activated charcoal. First-principles calculations show that the adsorption of CO(2) and CH(4) is more favored on BCN samples compared to graphene.
Stimuli-responsive organic-inorganic hybrid spheres were synthesized by coating the colloidal polystyrene spheres with polyelectrolyte-protected aminoclay, Mg phyllo(organo)silicate layers in a layer-by-layer method. The clay layers are sandwiched between the polyelectrolyte layers. The aminoclay swells in water due to protonation of amino groups, and the degree of swelling depends on the pH of the medium. As a result, the hybrid spheres undergo a size change up to 60% as the pH is changed from 9 to 4. The stimuli-responsive property of the hybrid spheres was used for the release of ibuprofen and eosin at different pH.
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