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31.
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   
32.
Automation and Remote Control - We consider multicriteria minimax optimization problems with criteria in the form of the maxima of functionals given by the induced norms of linear operators taking...  相似文献   
33.
Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Å2 was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R2=0.92) with an experimental measure of hydrogen bond donor potential, Δlog Poct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.  相似文献   
34.
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   
35.
Analog Integrated Circuits and Signal Processing - As the 5G era beckons in the world of communication and information technology, there is a surge in demand for battery-operated, mobile wireless...  相似文献   
36.
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu-Glu-CAB-2Mal.  相似文献   
37.
Theoretical Foundations of Chemical Engineering - Using gas–liquid chromatography, the activity coefficients upon the infinite dilution of the components of the reaction mixture for obtaining...  相似文献   
38.
Mobile Networks and Applications - Blockchain applications have continuously improved ever since its first debut on cryptocurrency. From then on, its uses have branched out from the financial...  相似文献   
39.
Journal of Signal Processing Systems - Convolutional Neural Networks (CNNs) have improved several computer vision applications, like object detection and classification, when compared to other...  相似文献   
40.
The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.  相似文献   
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