The focus of this study was on the effects of vitamin D stimulation of PBMCs immediately after their isolation. Since cell sorting induces stress to cells , the RNA-seq approach of this study captured only the bulk response of PBMCs, i.e., the heterogeneity of the cell population is masked. Thus, the most elegant approach would have been transcriptome profiling via single cell RNA-seq. However, the majority of the vitamin D target genes are primarily expressed in monocytes, i.e., the results presented in this study primarily reflect that of the monocyte fraction of PBMCs. A further limitation of this study is its focus on the transcrip- tome, which is only a limited proxy for protein levels . Thus, the findings of this study and their functional implications need to be confirmed with proteome-wide data and functional essays. Finally, while substantial differential expression only occurred after 8 h, a denser sampling at earlier time points would allow a more precise dissection between direct and indirect targets. This applies in particular to very early responding vitamin D target genes, such as G0S2, which display significant differential expression already after 4 h but their expression levels are not changing at later time points. Thus, some very early responding genes may have been mislabeled as indirect targets.In conclusion, this study describes the time-resolved transcriptional response of human PBMCs to vitamin D stimulation. This experimental design allows the segregation of the 662 vitamin D responding genes into primary, secondary, direct and indirect target genes. Prominent vitamin D targets are the clusters of the HLA, CXCL and S100A genes, which mediate inflammatory processes of the innate immune system as well as the response of the adaptive immune system.
After I turned in my Adam Smith book-manuscript to the press, I read Susan Wolf's wonderful essay, Moral Saints, because I had an intuition that the view I ascribed to Smith on virtue (in the book) has a kind of family resemblance to Wolf's position. (It does, actually.) In reading her piece I had that kind of disorientation when one meets a one-time friend--even if one returns to a mode of presentation that exhibits familiarity, one thereby simultaneously recognizes one is a different person than one had been. I actually wondered if I had read it before, or if I only had knowledge by description of it; because I had forgotten that she praises Katherine Hepburn (over Mother Teresa) and footnotes Orwell's essay in it. I am not the kind of person that ignores Hepburn or overlooks footnotes, and Wolf's essay has only six (and these include references to the usual suspects: Bernard Williams, Tom Nagel, Michael Stocker, and Kant).
This is not to say that Gandhi cannot be evaluated in light of standards he would not accept. Orwell shows us how that can be done with respect. (I have quoted the closing lines above.) Orwell emphasizes that Gandhi was a master of \"non-violent warfare, a way of defeating the enemy without hurting him and without feeling or arousing hatred.\" The absence of hatred and Gandhi's \"honesty\" -- by which Orwell means existential integrity, that is the words and actions match each other and one is willing to acknowledge the implications of one's commitments -- are the ruling themes of Orwell's essay. (Soon I will discuss Orwell's treatment of Gandhi's pacifism.) While Orwell insists that Gandhi's tactics and means are not appropriate in all contexts (\"Gandhi, who after all was born in 1869, did not understand the nature of totalitarianism\"), he also notes that Gandhi was \"shrewd\" enough to adjust means to context. 1e1e36bf2d