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  • Bryan Joensen heeft een update geplaatst 3 dagen, 8 uren geleden

    INTRODUCTION We investigated the mechanisms underlying immobilization-induced muscle pain in rats. METHODS In rat skeletal muscle, pressure pain threshold (PPT) of the gastrocnemius muscle was measured, and nerve growth factor (NGF) level, peripheral nerve fiber density, macrophage number, and interleukin-1β (IL-1β) mRNA expression were examined. An NGF receptor inhibitor was injected intramuscularly to assess the relationship between PPT and NGF levels. RESULTS Immobilization resulted in a decrease in PPT and increases in NGF level, C-fiber density, M1 macrophage number, and IL-1β mRNA expression. Injection of NGF receptor inhibitor reversed the decrease in PPT. DISCUSSION NGF upregulation may be a major contributor to immobilization-induced muscle pain. The increases in C-fiber density, M1 macrophage number, and IL-1β mRNA expression may be related to immobilization-induced muscle pain. © 2020 Wiley Periodicals, Inc.The gaseous plant hormone ethylene induces the ripening of climacteric fruit, including apple (Malus domestica). Another phytohormone, auxin, is known to promote ethylene production in many horticultural crops, but the regulatory mechanism remains unclear. Here, we found that auxin application induces ethylene production in apple fruit prior to the stage of commercial harvest, when they are not otherwise capable of ripening naturally. The expression of MdARF5, a member of the auxin response factor transcription factor (TF) family involved in the auxin signaling pathway, was enhanced by treatment with the synthetic auxin naphthaleneacetic acid (NAA). Further studies revealed that MdARF5 binds to the promoter of MdERF2, encoding a TF in the ethylene signaling pathway, as well as the promoters of two 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes (MdACS3a and MdACS1) and an ACC oxidase (ACO) gene, MdACO1, all of which encode key steps in ethylene biosynthesis, thereby inducing their expression. We also observed that auxin-induced ethylene production was dependent on the methylation of the MdACS3a promoter. Our findings reveal that auxin induces ethylene biosynthesis in apple fruit through activation of MdARF5 expression. This article is protected by copyright. All rights reserved.Tricin (3´,5´-dimethoxylated flavone) is a predominant flavonoid amongst monocots but occurs only in isolated and unrelated dicot lineages. Although tricin biosynthesis has been intensively studied in monocots, it remained largely elusive in tricin-accumulating dicots. We investigated a subgroup of cytochrome P450 (CYP) 75B subfamily flavonoid B-ring hydroxylases (FBHs) from two tricin-accumulating legumes, Medicago truncatula and alfalfa (M. sativa), by phylogenetic, molecular, biochemical and mutant analyses. Five Medicago cytochrome P450 CYP75B FBHs are phylogenetically distant from other legume CYP75B members. Among them, MtFBH-4, MsFBH-4 and MsFBH-10 were expressed in tricin-accumulating vegetative tissues. In vitro and in planta analyses demonstrated that these proteins catalyze 3´- and 5´-hydroxylations critical to tricin biosynthesis. A key amino acid polymorphism, T492G, at their Substrate Recognition Site 6 domain is required for the novel 5´-hydroxylation activities. M. 3,4-Dichlorophenyl isothiocyanate research buy truncatula mtfbh-4 mutants were tricin-deficient, indicating that MtFBH-4 is indispensable for tricin biosynthesis. Our results revealed that these Medicago legumes had acquired the tricin pathway through molecular evolution of CYP75B FBHs subsequent to speciation from other non-tricin-accumulating legumes. Moreover, their evolution is independent from that of grass-specific CYP75B apigenin 3´-hydroxylases/chrysoeriol 5´-hydroxylases dedicated to tricin production and Asteraceae CYP75B flavonoid 3´,5´-hydroxylases catalyzing the production of delphinidin-based pigments. This article is protected by copyright. All rights reserved.AIMS PDGFRB rearrangement defines a unique group of myeloid/lymphoid neoplasms with frequent eosinophilia and high sensitivity to tyrosine kinase inhibitors. This genetic abnormality is also rarely reported in Philadelphia-like B-lymphoblastic leukemia (B-ALL). PDGFRB rearrangement was initially thought to only occur in cases with 5q31-33 rearrangement by conventional cytogenetics; however, there are reported cases with cryptic rearrangements, suggesting the need for a broader screening strategy. METHODS AND RESULTS We performed FISH for PDGFRB rearrangement in 197 patients, including 70 B-ALL, 10 myeloid neoplasms with 5q31-33 rearrangements, and 117 with eosinophilia (≥0.5 x 109 /L in peripheral blood or ≥ 5% in bone marrow), and identified PDGFRB rearrangement in 4/197 (2.0%) cases. In an attempt to identify clinicopathologic and genetic features that may have a stronger association with PDGFRB rearrangement, we analyzed 13 patients with confirmed PDGFRB rearrangements, including 10 myeloid neoplasms and 3 B-ALL. Of the 10 patients with myeloid neoplasms, eosinophilia was present in 8, monocytosis in 2, 5q31-33 rearrangement in 7, and abnormal bone marrow morphology in all. All patients with myeloid neoplasms showed an excellent response to imatinib including a patient in blast crisis. The three B-ALL patients presented de novo, showed no eosinophilia, had complex karyotype including 5q31-33 rearrangement, and had clinically aggressive courses with ultimate patient demise. CONCLUSIONS These findings suggest a higher yield for the identification of PDGFRB rearrangement may result from an index of suspicion on patients with eosinophilia, monocytosis, bone marrow features of a myeloid neoplasm, 5q31-33 rearrangement, and patients with Philadelphia-like B-ALL. This article is protected by copyright. All rights reserved.BACKGROUND Healthcare professionals (HCPs) play an important role in discussing weight with children and their parents but report barriers such as lack of training and supports. These barriers are especially prevalent within specialized populations such as children with autism spectrum disorder (ASD). To address this, a Knowledge Translation Casebook on positive weight-related conversations was developed by a research team at a Canadian paediatric hospital. The purpose of the current pre-implementation pilot study was to explore initial acceptability and adoption of the Casebook into clinical settings. METHODS An interactive, multimodal education workshop was created to provide HCPs with knowledge and training on how to have positive weight-related conversations with children and parents. Two workshops were conducted using the same curriculum but delivered either in-person or online. Participants were drawn from a team of clinicians at a teaching hospital whose care focuses on medication management for clients with ASD and clinicians participating in a distance learning programme on best practice care for clients with ASD.

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