1.Immunosuppression and Neuroinflammation in Stroke Pathobiology
Qian JIANG ; Christopher R. STONE ; Kenneth ELKIN ; Xiaokun GENG ; Yuchuan DING
Experimental Neurobiology 2021;30(2):101-112
Over the preceding decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. One such advance has been an increased understanding of the multifarious crosstalk in which the nervous and immune systems engage in order to maintain homeostasis. By interrupting the immune-nervous nexus, it is thought that stroke induces change in both systems. Additionally, it has been found that both innate and adaptive immunosuppression play protective roles against the effects of stroke. The release of danger-/damage-associated molecular patterns (DAMPs) activates Toll-like receptors (TLRs), contributing to the harmful inflammatory effects of ischemia/reperfusion injury after stroke; the Tyro3, Axl, and MerTK (TAM)/Gas6 system, however, has been shown to suppress inflammation via downstream signaling molecules that inhibit TLR signaling. Anti-inflammatory cytokines have also been found to promote neuroprotection following stroke. Additionally, adaptive immunosuppression merits further consideration as a potential endogenous protective mechanism. In this review, we highlight recent studies regarding the effects and mechanism of immunosuppression on the pathophysiology of stroke, with the hope that a better understanding of the function of both of innate and adaptive immunity in this setting will facilitate the development of effective therapies for post-stroke inflammation.
2.Immunosuppression and Neuroinflammation in Stroke Pathobiology
Qian JIANG ; Christopher R. STONE ; Kenneth ELKIN ; Xiaokun GENG ; Yuchuan DING
Experimental Neurobiology 2021;30(2):101-112
Over the preceding decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. One such advance has been an increased understanding of the multifarious crosstalk in which the nervous and immune systems engage in order to maintain homeostasis. By interrupting the immune-nervous nexus, it is thought that stroke induces change in both systems. Additionally, it has been found that both innate and adaptive immunosuppression play protective roles against the effects of stroke. The release of danger-/damage-associated molecular patterns (DAMPs) activates Toll-like receptors (TLRs), contributing to the harmful inflammatory effects of ischemia/reperfusion injury after stroke; the Tyro3, Axl, and MerTK (TAM)/Gas6 system, however, has been shown to suppress inflammation via downstream signaling molecules that inhibit TLR signaling. Anti-inflammatory cytokines have also been found to promote neuroprotection following stroke. Additionally, adaptive immunosuppression merits further consideration as a potential endogenous protective mechanism. In this review, we highlight recent studies regarding the effects and mechanism of immunosuppression on the pathophysiology of stroke, with the hope that a better understanding of the function of both of innate and adaptive immunity in this setting will facilitate the development of effective therapies for post-stroke inflammation.
3.YPED:An Integrated Bioinformatics Suite and Database for Mass Spectrometry-based Proteomics Research
Colangelo M. CHRISTOPHER ; Shifman MARK ; Cheung KEI-HOI ; Stone L. KATHRYN ; Carriero J. NICHOLAS ; Gulcicek E. EROL ; Lam T. TUKIET ; Wu TERENCE ; Bjornson D. ROBERT ; Bruce CAN ; Nairn C. ANGUS ; Rinehart JESSE ; Miller L. PERRY ; Williams R. KENNETH
Genomics, Proteomics & Bioinformatics 2015;(1):25-35
We report a significantly-enhanced bioinformatics suite and database for proteomics research called Yale Protein Expression Database (YPED) that is used by investigators at more than 300 institutions worldwide. YPED meets the data management, archival, and analysis needs of a high-throughput mass spectrometry-based proteomics research ranging from a single laboratory, group of laboratories within and beyond an institution, to the entire proteomics com-munity. The current version is a significant improvement over the first version in that it contains new modules for liquid chromatography–tandem mass spectrometry (LC–MS/MS) database search results, label and label-free quantitative proteomic analysis, and several scoring outputs for phosphopeptide site localization. In addition, we have added both peptide and protein comparative analysis tools to enable pairwise analysis of distinct peptides/proteins in each sample and of overlapping peptides/proteins between all samples in multiple datasets. We have also implemented a targeted proteomics module for automated multiple reaction monitoring (MRM)/selective reaction monitoring (SRM) assay development. We have linked YPED’s database search results and both label-based and label-free fold-change analysis to the Skyline Panorama repository for online spectra visualization. In addition, we have built enhanced functionality to curate peptide identifications into an MS/MS peptide spectral library for all of our protein database search identification results.