Medical School Rankings-Bad for the Health of the Profession and the Public.

This Viewpoint discusses the limitations of medical school ranking in attracting a diverse student population and urges administrators to holistically communicate their mission, goals, and learning environment as an alternative strategy.

Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice.

BACKGROUND: We have recently demonstrated that polysaccharides from fruiting body extract (FBE) or mycelia extract (ME) of the edible mushroom Pleurotus pulmonarius exert antiproliferative effects in intestinal cells and an anti-inflammatory effect in a dextran sulfate sodium (DSS) mouse model of acute colitis. The aim of this study was to assess the role of fungal FBE and ME in colon carcinogenesis. METHODS: In vitro, human colorectal cancer cells were treated with FBE and ME and analyzed for inflammation response, for markers of apoptosis, and for cell-cycle progression. In vivo, FBE and ME were tested in a mouse model of colitis-associated colorectal carcinogenesis induced by cyclic treatments with DSS and azoxymethane. Treated mice were fed a daily diet containing 2 or 20 mg FBE or ME per mouse for 80 days. RESULTS: In vitro, FBE and ME induced apoptosis in a dose-responsive manner and modulated the expression of Bcl-2, Bax, and cytochrome c, and blocked tumor necrosis factor (TNF)-α-induced inhibitor of nuclear factor (NF) (Iκ)-Bα degradation and NF-κB nuclear translocation. In vivo, dietary administration of FBE and ME significantly reduced the formation of aberrant crypt foci, which precedes colorectal cancer, and of microadenomas. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon. Additionally, FBE and ME inhibited the expression of the proinflammatory cytokine TNF-α in colonic tissue. CONCLUSIONS: We conclude that P. pulmonarius FBE and ME inhibit colitis-associated colon carcinogenesis induced in mice through the modulation of cell proliferation, induction of apoptosis, and inhibition of inflammation.

Release of Pleurotus ostreatus versatile-peroxidase from Mn2+ repression enhances anthropogenic and natural substrate degradation.

The versatile-peroxidase (VP) encoded by mnp4 is one of the nine members of the manganese-peroxidase (MnP) gene family that constitutes part of the ligninolytic system of the white-rot basidiomycete Pleurotus ostreatus (oyster mushroom). VP enzymes exhibit dual activity on a wide range of substrates. As Mn(2+) supplement to P. ostreatus cultures results in enhanced degradation of recalcitrant compounds and lignin, we examined the effect of Mn(2+) on the expression profile of the MnP gene family. In P. ostreatus (monokaryon PC9), mnp4 was found to be the predominantly expressed mnp in Mn(2+)-deficient media, whereas strongly repressed (to approximately 1%) in Mn(2+)-supplemented media. Accordingly, in-vitro Mn(2+)-independent activity was found to be negligible. We tested whether release of mnp4 from Mn(2+) repression alters the activity of the ligninolytic system. A transformant over-expressing mnp4 (designated OEmnp4) under the control of the ß-tubulin promoter was produced. Now, despite the presence of Mn(2+) in the medium, OEmnp4 produced mnp4 transcript as well as VP activity as early as 4 days after inoculation. The level of expression was constant throughout 10 days of incubation (about 0.4-fold relative to ß-tubulin) and the activity was comparable to the typical activity of PC9 in Mn(2+)-deficient media. In-vivo decolorization of the azo dyes Orange II, Reactive Black 5, and Amaranth by OEmnp4 preceded that of PC9. OEmnp4 and PC9 were grown for 2 weeks under solid-state fermentation conditions on cotton stalks as a lignocellulosic substrate. [(14)C]-lignin mineralization, in-vitro dry matter digestibility, and neutral detergent fiber digestibility were found to be significantly higher (about 25%) in OEmnp4-fermented substrate, relative to PC9. We conclude that releasing Mn(2+) suppression of VP4 by over-expression of the mnp4 gene in P. ostreatus improved its ligninolytic functionality.