AMPK controls the regenerative programme of DRG sensory neurons after injury

Regeneration after injury occurs in axons that lie in the peripheral nervous system but it fails in the central nervous system limiting functional recovery. Despite recent progress, to date we ignore the molecular identity of peripheral versus central projecting axons that might underpin this differential regenerative ability. To fill this knowledge gap, here we combined axoplasmic proteomics from sciatic or centrally projecting branches of L4-6 DRG with RNAseq to compare axonal and cell body responses between a regeneration-incompetent central spinal versus regeneration-competent peripheral sciatic nerve injury. This allowed identifying for the first time signalling pathways uniquely represented in peripheral versus central projecting L4- 6 DRG axons, including prior and subsequent to an injury. Next, RNAseq and proteomics network and pathway analysis suggested AMPK as master regulator controlling axonal regenerative signalling pathways. AMPK immunoprecipitation followed by mass spectrometry from DRG suggested that the 26S proteasome and the 26S regulatory subunit PSMC5 are preferentially bound to AMPKα for proteosomal degradation following sciatic axotomy. Mechanistically, we found that phosphorylation of proteosomal subunit PSMC5 and injury activated CaMKIIα are required for AMPKα1 degradation after sciatic injury. Moreover, ubiquitin E3 ligase Trim28 regulates AMPKα1 expression. Finally, conditional deletion of AMPKα1 promotes multiple regenerative signals, axonal regeneration and functional recovery of sensory axons across the injured spinal cord, suggesting inhibition of AMPK as novel regenerative target following spinal injury

Atomically homogeneous dispersed ZnO/N-doped nanoporous carbon composites with enhanced CO2 uptake capacities and high efficient organic pollutants removal from water

Author's manuscript version. The final published version is available from the publisher via doi:10.1016/j.carbon.2015.08.015Copyright © 2015 Elsevier Ltd. All rights reserved.Article first available online - 8th August 2015Advanced functional composite of ZnO nanoparticles embedded in N-doped nanoporous carbons has been synthesized by a simple one-step carbonization of zeolitic imidazolate framework-8 under a water stream atmosphere. A variety of characterization techniques show that the introduction of water steam during the carbonization process holds the key to obtain the fine and homogeneously dispersed ZnO nanoparticles within the functionalised nanoporous carbon matrix. Possessing a higher specific surface area, a larger pore volume and abundant oxygen-containing hydrophilic functional groups, the resulting composite exhibits a stronger interaction with CO2 and is more efficient to promote the photocatalytic degradation-adsorption of methylene blue under visible light than the composite obtained without steam treatment. As a result, the steam derived composite exhibits increased CO2 uptake capacity and excellent methylene blue molecules removal from water. Using different metal-organic frameworks as precursors, this new, simple and green method can be further expanded to generate various new homogeneous dispersed functional metal oxide/porous carbon composites with high efficiency in relevant applications. © 2015 Elsevier Ltd.Royal SocietyRoyal Academy of Engineerin

Integrated metabolomics and lipidomics evaluate the alterations of flavor precursors in chicken breast muscle with white striping symptom

White striping (WS) is the most common myopathy in the broiler chicken industry. To reveal flavor changes of WS meat objectively, flavor precursors of WS breast muscle were evaluated systematically with integrated metabolomics and lipidomics. The results showed that WS could be distinguished from normal controls by E-nose, and four volatile compounds (o-xylene, benzene, 1,3-dimethyl, 2-heptanone and 6-methyl and Acetic acid and ethyl ester) were detected as decreased compounds by gas chromatography-mass spectrometry. Lipidomic analysis showed that WS breast fillets featured increased neutral lipid (83.8%) and decreased phospholipid molecules (33.2%). Targeted metabolomic analysis indicated that 16 hydrophilic metabolites were altered. Thereinto, some water-soluble flavor precursors, such as adenosine monophosphate, GDP-fucose and L-arginine increased significantly, but fructose 1,6-bisphosphate and L-histidine significantly decreased in the WS group. These results provided a systematic evaluation of the flavor precursors profile in the WS meat of broiler chickens

Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models

Cyclin-dependent-like kinase 5 (Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signaling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder