Impact of reactive oxygen species (ROS) in development of hyperalgesia has recently motivated scientists to focus on ROS as novel target of anti-hyperalgesic interventions. Studies have indicated the usefulness of ROS scavengers and exogenous antioxidants as anti-nociceptive agents in animal models of neuropathic and inflammatory hyperalgesia. In present study, we suggest the anti-hyperalgesic potential of the dietary antioxidant quercetin on chronic inflammatory hyperalgesia induced by Complete Freund's Adjuvant (CFA). Three doses of quercetin (25, 50 and 75 mg/kg body weight) for consecutive 7 days were used for the study. Thermal hyperalgesia was assessed by paw withdrawal latency (PWL) test and inflammation was checked in terms of changes in paw edema. The insight of molecular signaling during chronic hyperalgesia was analyzed by TNF-α-TNFR1-ERK1/2 pathway in relation to change in ROS level in DRG and spinal cord. CFA-induced hyperalgesia was confirmed by decreased PWL and increased c-Fos activity in dorsal horn of spinal cord, determined by immunohistochemical analysis. It was characterized with elevated level of ROS and TNF-α estimated by ELISA. The activation of ERK1/2 and NF-κB in DRG and spinal cord and over-expression of TNFR1 in DRG were analyzed by Western blotting. Up-regulation of Iba1 and GFAP indicates glial activation in spinal cord. Expression of GFAP and its co-localization with NF-κB were examined by immunofluorescence. All the molecular modulators of hyperalgesia were brought towards normal after quercetin treatment showing its anti-hyperalgesic activity, indicating that repeated quercetin treatment is able to alleviate chronic inflammatory hyperalgesia by attenuating TNF-α-TNFR1-ERK1/2 signaling pathway via modulation of ROS and by suppression of central sensitization via inhibition of spinal glial activation.Cone-beam computed tomography (CBCT) is an important imaging modality for image-guided radiotherapy and adaptive radiotherapy. Feldkamp-Davis-Kress (FDK) method is widely adopted in clinical CBCT reconstructions due to its fast and robust application. While iterative algorithms have been shown to outperform FDK techniques in reducing noise and imaging dose, they are unable to correct projection-domain artefacts such as beam hardening and scatter. Empirical correction techniques require a holistic approach as beam hardening and scatter coexist in the measurement data. This multi-part proof of concept study conducted in MATLAB presents a novel approach to artefact reduction for CBCT image reconstruction. Firstly, we decoupled the beam hardening and scatter contributions originating from the imaging object and the bowtie filter. Next, a model was constructed to apply pixel-wise corrections to separately account for artefacts induced by the imaging object and the bowtie filter, in order to produce mono-energetic equivalent and scatter-compensated projections. Finally, the effectiveness of the correction model was tested on an offset phantom scan as well as a clinical brain scan. A conjugate-gradient least-squares algorithm was implemented over five iterations using FDK result as the initial input. Our proposed correction model was shown to effectively reduce cupping and shading artefacts in both phantom and clinical studies. This simple yet effective correction model could be readily implemented by physicists seeking to explore the benefits of iterative reconstruction.The phytohormone ethylene is widely involved in many developmental processes and is a crucial regulator of defense responses against biotic and abiotic stresses in plants. Ethylene-responsive element binding protein, a member of the APETALA2/ethylene response factor (AP2/ERF) superfamily, is a transcription factor that regulates stress-responsive genes by recognizing a specific cis-acting element of target DNA. A previous study showed only the NMR structure of the AP2/ERF domain of AtERF100 in complex with a GCC box DNA motif. In this report, we determined the crystal structure of AtERF96 in complex with a GCC box at atomic resolution. We analyzed the binding residues of the conserved AP2/ERF domain in the DNA recognition sequence. In addition to the AP2/ERF domain, an N-terminal α-helix of AtERF96 participates in DNA interaction in the flanking region. We also demonstrated the structure of AtERF96 EDLL motif, a unique conserved motif in the group IX of AP2/ERF family, might involve in the transactivation of defense-related genes. Our study establishes the structural basis of the AtERF96 transcription factor in complex with the GCC box, as well as the DNA binding mechanisms of the N-terminal α-helix and AP2/ERF domain.
  A sugarcane MYB present in the culm induces suberin biosynthesis and is involved both with fatty acid and phenolics metabolism. Few transcription factors have been described as regulators of cell wall polymers deposition in C4 grasses. Particularly, regulation of suberin biosynthesis in this group of plants remains poorly understood. Here, we showed that the sugarcane MYB transcription factor ShMYB78 is an activator of suberin biosynthesis and deposition. ShMYB78 was identified upon screening genes whose expression was upregulated in sugarcane internodes undergoing suberization during culm development or triggered by wounding. Agrobacterium-mediated transient expression of ShMYB78 in Nicotiana benthamiana leaves induced the ectopic deposition of suberin and its aliphatic and aromatic monomers. Further, the expression of suberin-related genes was induced by ShMYB78 heterologous expression in Nicotiana benthamiana leaves. ShMYB78 was shown to be a nuclear protein based on its presence in sugarcane internode nm development or triggered by wounding. Agrobacterium-mediated transient expression of ShMYB78 in Nicotiana benthamiana leaves induced the ectopic deposition of suberin and its aliphatic and aromatic monomers. Further, the expression of suberin-related genes was induced by ShMYB78 heterologous expression in Nicotiana benthamiana leaves. ShMYB78 was shown to be a nuclear protein based on its presence in sugarcane internode nuclear protein extracts, and protoplast transactivation assays demonstrated that ShMYB78 activates the promoters of the sugarcane suberin biosynthetic genes β-ketoacyl-CoA synthase (ShKCS20) and caffeic acid-O-methyltransferase (ShCOMT).  https://www.selleckchem.com/products/fluoxetine.html  Our results suggest that ShMYB78 may be involved in the transcriptional regulation of suberin deposition, from fatty acid metabolism to phenylpropanoid biosynthesis, in sugarcane internodes.