F. Scott Fitzgerald : his materials and his methods

From the time I was first introduced to Fitzgerald\u27s writing through a reading of This Side of Paradise, when I was a freshman in college, his subject matter and technique as a novelist have interested me intensely. After reading the first novel, I was not satisfied until I had voraciously read his other novels. With each reading of another of his books, my interest increased. Later, when Mizener\u27s valuable biography appeared, I was introduced to Fitzgerald the man and have found his life as fascinating as his writings. However I felt that none of the books about Fitzgerald completely presented the carry-over of living material from his own experiences to his novels; nor were his techniques employed in novel writing fully examined

Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity

Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.</p