Southern Illinois University School of Medicine

About: Southern Illinois University School of Medicine is a education organization based out in Springfield, Illinois, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 3747 authors who have published 5977 publications receiving 209115 citations. The organization is also known as: SIU School of Medicine.

Pathologic changes associated with intracranial hypotension and meningeal enhancement On MRI

Abstract: We report a patient with a 6-week history of postural headache due to intracranial hypotension whose MRI revealed findings typical of this syndrome, including diffuse meningeal enhancement following gadolinium infusion. Biopsy revealed extensive fibrocollagenous proliferation in the leptomeninges without evidence of inflammation. The pathologic changes in this patient, which occurred soon after the onset of symptoms, are probably related to the striking meningeal enhancement seen in this syndrome.

Ctk complex-mediated regulation of histone methylation by COMPASS.

Abstract: A comparative global proteomic screen identified factors required for COMPASS (complex of proteins associated with Set1)-mediated mono-, di-, and trimethylation of the fourth lysine of histone H3 (H3K4), which included components of a cyclin-dependent protein kinase (Ctk complex) that phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (Pol II). Our results indicate that histone H3K4 methylation levels are regulated by the Ctk1, Ctk2, and Ctk3 components of the Ctk complex. We show that loss of Ctk1 kinase activity results in reduced histone H3K4 monomethylation levels, followed by a global increase in histone H3K4 trimethylation levels on chromatin. Ctk1 loss does not appear to have a substantial effect on histone H2B monoubiquitination levels or COMPASS and Paf1 complex phosphorylation. Our chromatin immunoprecipitation studies demonstrate that histone H3 eviction during active transcription is decelerated in a CTK1 deletion strain in response to reduced levels of Pol II recruitment. Our in vitro studies show that the onset of monomethylation on an unmethylated histone H3 by COMPASS is virtually immediate, while the onset of trimethylation occurs upon extended time of association between the histone tail and COMPASS. Our study suggests a role for the Ctk complex in the regulation of the pattern of H3K4 mono-, di-, and trimethylation via COMPASS.

The role of short-chain fatty acids in orchestrating two types of programmed cell death in colon cancer.

Abstract: Short-chain fatty acids are the major by-products of bacterial fermentation of undigested fibers in the colon. SCFAs, mostly propionate and butyrate, induce differentiation, growth arrest, and apoptosis in colon cancer cells. The anticancer effect of SCFAs is also supported by epidemiological studies suggesting an inverse relationship between the level of dietary fibers and the incidence of human colon cancer. Dietary components influence the risk of human colon cancer including colon cancer through diverse mechanisms, which include the activation or inhibition of autophagy (type II programmed cell death (PCD)). Herein we demonstrate that propionate and butyrate induce autophagy in human colon cancer cells to dampen apoptosis, whereas inhibition of autophagy potentiates SCFA-induced apoptosis. The propionate-induced autophagy originates from mitochondria defects associated with cellular ATP depletion and ROS generation, both of which contribute to AMPK activation and consequential mTOR inhibition. Remarkably, when autophagy is suppressed through either pharmacological or genetic approaches, the colon cancer cells become sensitized toward propionate-induced apoptotic cell death (type I PCD). Our study is the first report characterizing this novel role of SCFAs in orchestrating two types of programmed cell death. The observed pro-survival effects of autophagy in retarding mitochondria-mediated apoptosis suggest that application of an autophagy inhibitor might improve the therapeutic efficacy of SCFAs in inducing colon cancer suppression.