The phosphorylation of serine 10 in histone 3 (p-S10H3) has recently been demonstrated to participate in spinal nociceptive processing. However, superficial dorsal horn (SDH) neurons involved in p-S10H3-mediated nociception have not been fully characterized. In the present work, we combined immunohistochemistry, in situ hybridization with the retrograde labeling of projection neurons to reveal the subset of dorsal horn neurons presenting an elevated level of p-S10H3 in response to noxious heat (60 °C), causing burn injury. Projection neurons only represented a small percentage (5%) of p-S10H3-positive cells, while the greater part of them belonged to excitatory SDH interneurons. The combined immunolabeling of p-S10H3 with markers of already established interneuronal classes of the SDH revealed that the largest subset of neurons with burn injury-induced p-S10H3 expression was dynorphin immunopositive in mice. Furthermore, the majority of p-S10H3-expressing dynorphinergic neurons proved to be excitatory, as they lacked Pax-2 and showed Lmx1b-immunopositivity. Thus, we showed that neurochemically heterogeneous SDH neurons exhibit the upregulation of p-S10H3 shortly after noxious heat-induced burn injury and consequential tissue damage, and that a dedicated subset of excitatory dynorphinergic neurons is likely a key player in the development of central sensitization via the p-S10H3 mediated pathway. 相似文献
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets. 相似文献
Probabilistic topic modeling algorithms like Latent Dirichlet Allocation (LDA) have become powerful tools for the analysis of large collections of documents (such as papers, projects, or funding applications) in science, technology an innovation (STI) policy design and monitoring. However, selecting an appropriate and stable topic model for a specific application (by adjusting the hyperparameters of the algorithm) is not a trivial problem. Common validation metrics like coherence or perplexity, which are focused on the quality of topics, are not a good fit in applications where the quality of the document similarity relations inferred from the topic model is especially relevant. Relying on graph analysis techniques, the aim of our work is to state a new methodology for the selection of hyperparameters which is specifically oriented to optimize the similarity metrics emanating from the topic model. In order to do this, we propose two graph metrics: the first measures the variability of the similarity graphs that result from different runs of the algorithm for a fixed value of the hyperparameters, while the second metric measures the alignment between the graph derived from the LDA model and another obtained using metadata available for the corresponding corpus. Through experiments on various corpora related to STI, it is shown that the proposed metrics provide relevant indicators to select the number of topics and build persistent topic models that are consistent with the metadata. Their use, which can be extended to other topic models beyond LDA, could facilitate the systematic adoption of this kind of techniques in STI policy analysis and design.
Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K2O-26.9CaO-46.1SiO2-2.6P2O5 mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration. 相似文献
The present study reports for the first time the performance of silver phosphate (Ag3PO4) microcrystals as photocatalyst (degradation of Rodamine B-RhB) and antifungal agent (against Candida albicans–C. albicans) under visible-light irradiation (455 nm). Ag3PO4 microcrystals were synthesized by a simple co-precipitation (CP) method at room temperature. The structural and electronic properties of the as-synthetized Ag3PO4 have been investigated before and after 4 cycles of RhB degradation under visible light using X-ray diffraction (XRD), micro-Raman spectroscopy, UV–Vis spectrophotometer and field emission scanning electron microscopy (FE-SEM) images. The antifungal activity was analyzed in planktonic cells and 48h-biofilm of C. albicans by colony forming units (CFU) counting, confocal laser and FE-SE microscopies. Statistical analysis was carried out using SPSS software. Morphological and structural modifications of Ag3PO4 were observed upon recycling. After 4 recycles, the material maintained its photodegradation property; an eightfold increase in the efficiency of Ag3PO4 was observed in planktonic cells and a two fold increase in biofilm when irradiated under visible light. Thus, higher antifungal effectiveness against C. albicans was obtained when associated with visible-light irradiation. 相似文献
Multimedia Tools and Applications - The design of robots capable of operating autonomously in changing and unstructured environments, requires using complex software architectures in which,... 相似文献
Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain–Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival. 相似文献