Observations on the Age and Growth of the Northern Pike, Esox Lucius L., in East Harbor, Ohio

Author Institution: Ohio Division of Wildlife, Columbus, Ohio and 2004 Sunrise Ave., Portsmouth, Ohi

Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed

Calcineurin as a Multifunctional Regulator: Unraveling Novel Functions in Fungal Stress Responses, Hyphal Growth, Drug Resistance, and Pathogenesis.

Calcineurin signaling plays diverse roles in fungi in regulating stress responses, morphogenesis and pathogenesis. Although calcineurin signaling is conserved among fungi, recent studies indicate important divergences in calcineurin-dependent cellular functions among different human fungal pathogens. Fungal pathogens utilize the calcineurin pathway to effectively survive the host environment and cause life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making targeting calcineurin a promising antifungal drug development strategy. Here we summarize current knowledge on calcineurin in yeasts and filamentous fungi, and review the importance of understanding fungal-specific attributes of calcineurin to decipher fungal pathogenesis and develop novel antifungal therapeutic approaches

Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed

Calcineurin-Mediated Regulation of Hyphal Growth, Septation, and Virulence in Aspergillus fumigatus.

Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic (CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens utilize the calcineurin pathway to survive in the host environment and cause life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making calcineurin a promising antifungal drug target. Here, we review novel findings on calcineurin localization and functions in Aspergillus fumigatus hyphal growth and septum formation through regulation of proteins involved in cell wall biosynthesis. Extensive mutational analysis in the functional domains of A. fumigatus CnaA has led to an understanding of the relevance of these domains for the localization and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode of calcineurin regulation by phosphorylation in filamentous fungi was found to be responsible for virulence in A. fumigatus. This finding of a filamentous fungal-specific mechanism controlling hyphal growth and virulence represents a potential target for antifungal therapy

The combined effects of high-energy shock waves and cytostatic drugs or cytokines on human bladder cancer cells.

The effects of shock waves generated by an experimental Siemens lithotripter in combination with cytostatic drugs or cytokines on several bladder cancer cell lines were examined in vitro. Proliferation after treatment was determined with the 3-4,5-dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug and each shock wave application mode in order to characterise the sensitising effect of shock wave pretreatment. The influence of the time between shock wave and drug treatment as well as the effects of different sequences of shock wave and drug treatment or concomitant treatment were assessed for selected combinations of cell lines and drugs. It was found that shock wave treatment could render certain cell lines more susceptible to subsequent cis-platinum, mitomycin C or actinomycin D incubation. Cell lines sensitive to tumour necrosis factor alpha or interferon alpha were further sensitised to these cytokines by shock wave pretreatment. The enhanced sensitivity to cis-platinum and actinomycin D decreased rapidly during the first hours after shock wave treatment. The antiproliferative effect was most pronounced after concomitant shock wave and drug treatment. The sensitisation to interferon alpha diminishes more slowly after shock wave exposure. From the results presented in this study it is concluded that transient shock wave-induced permeabilisation of cell membrane not only enhances drug efficiency, but also causes damage to cell organelles and alterations in cellular metabolism

Shoe rim and shoe buckle pseudotumor of the ankle in elite and professional figure skaters and snowboarders: MR imaging findings

Objective: To review MR imaging of figure skaters and snowboarders presenting with painful soft-tissue swelling of the lateral supramalleolar region with a clinical provisional diagnosis of soft-tissue tumor. Design and patients: MR imaging was prospectively reviewed by two sub-specialized musculoskeletal radiologists. The findings were correlated with a second clinical review and examination of the shoe wear. The patients were four female athletes undergoing heavy training regimes, ranging in age between 16 and 25years. Two patients were elite figure skaters, and two were professional snowboarders. Three patients had unilateral masses with pain, and one patient presented with bilateral clinical findings. Results: MR imaging showed subcutaneous, focal soft-tissue masses of the supramalleolar region in five ankles at the same level above the ankle joint. MR imaging prompted a second clinical review and correlation with the shoe wear. The MR imaging findings correlated to the level of the shoe rim or shoe buckle in all patients, confirming the suspected MR imaging diagnosis of an impingement syndrome. All four sportswomen were training excessively, ignoring safety advice regarding training duration, timing of breaks, and shoe wear rotation. Conclusion: Ice skaters and snowboarders may present with persistent and disabling pain. On MR imaging, this corresponds to a focal soft-tissue abnormality, which may be due to subcutaneous fat impingement between the fibula and the shoe rim or shoe buckl