An shRNA-Based Screen of Splicing Regulators Identifies SFRS3 as a Negative Regulator of IL-1β Secretion

The generation of diversity and plasticity of transcriptional programs are key components of effective vertebrate immune responses. The role of Alternative Splicing has been recognized, but it is underappreciated and poorly understood as a critical mechanism for the regulation and fine-tuning of physiological immune responses. Here we report the generation of loss-of-function phenotypes for a large collection of genes known or predicted to be involved in the splicing reaction and the identification of 19 novel regulators of IL-1β secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1β secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1β secretion due to elevation of IL-1β and caspase-1 mRNA in addition to active caspase-1 levels. This study points to the relevance of splicing in the regulation of auto-inflammatory diseases

Synthesis of 1-phathalimidoalkane phosphonate

Phosphonylation of RCHO with HP(O)​(OEt)​2 gave RCH(OH)​P(O)​(OEt)​2 which condensed with phthalimide to give 60-​71​% I [R = H, Me, Pr, Me(CH2)​5, Me(CH2)​6]​

UNUSUAL RING-OPENING REACTION OF 6,7-DIHYDROTHIENO[3,2-D]PYRIMIDINE-2,4-DIONE DERIVATIVES LEADING TO 5-(ALKYLTHIO)-6-VINYLURACILS

Our previous studies on 4-cyano- and 44methoxycarbonyl) thiolan-3-one, two sulfur-containing heterocycles usually utilized for the preparation of heteropolycyclic systems, led us to discover that their anions serve efficiently as synthetic equivalents of a-acrylate and a-acrylonitrile anions, respectively, allowing interesting synthetic application^

Synthesis of 3-Substituted 7-Methyl-5H-pyrazole[4,3-d]-1,2,3-triazin- 4(3H)-ones and Amide-N-Substituted 3-Methyl-4-diazopyrazole-5-carboxamides

Diazotization of amide-N-substituted 4-amino-3-methylpyrazole-5-carboxamides 4 with sodium nitrite and acetic acid produces 3-substituted 7-methyl-5H-pyrazolo[4,3-d]-1,2,3-triazin-4(3H)-ones 6 or amide-N-substituted 3-methyl-4-diazopyrazole-5-carboxamides 5, depending on the substitution pattern. © 1988 Georg Thieme Verlag. All rights reserved