Project description:Divergent functions of two clades of flavodoxin in diatoms mitigate oxidative stress and iron limitation Thalassiosira pseudonana and 4 open-ocean diatoms were subjected to iron limitation or short-term oxidative stress (hydrogen peroxide). mRNA profiles of T. pseudonana (CCMP1335), Thalassiosira oceanica (CCMP1005), Amphora coffeaeformis (CCMP1405), Chaetoceros sp. (CCMP199), and Cylindrotheca closterium (CCMP340).
Project description:Phytoplankton and bacteria form the base of marine ecosystems and their interactions drive global biogeochemical cycles. The effect of bacteria and bacteria-produced compounds on diatoms range from synergistic to pathogenic and can affect the physiology and transcriptional patterns of the interacting diatom. Here, we investigate physiological and transcriptional changes in the marine diatom Thalassiosira pseudonana induced by extracellular metabolites of a known antagonistic bacterium Croceibacter atlanticus. Mono-cultures of C. atlanticus released compounds that inhibited diatom cell division and elicited a distinctive phenotype of enlarged cells with multiple plastids and nuclei, similar to what was observed when the diatom was co-cultured with the live bacteria. The extracellular C. atlanticus metabolites induced transcriptional changes in diatom pathways that include recognition and signaling pathways, cell cycle regulation, carbohydrate and amino acid production, as well as cell wall stability. Phenotypic analysis showed a disruption in the diatom cell cycle progression and an increase in both intra- and extracellular carbohydrates in diatom cultures after bacterial exudate treatment. The transcriptional changes and corresponding phenotypes suggest that extracellular bacterial metabolites, produced independently of direct bacterial-diatom interaction, may modulate diatom metabolism in ways that support bacterial growth.
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs.
Project description:In addition to their role in the development and function of the reproductive system, estrogens have significant anti-inflammatory properties. Although both estrogen receptors (ERs) can mediate anti-inflammatory actions, ERbeta is a more desirable therapeutic target because ERalpha mediates the proliferative effects of estrogens on the mammary gland and uterus. In fact, selective ERbeta agonists have beneficial effects in preclinical models involving inflammation without causing growth-promoting effects on the uterus or mammary gland. However, their mechanism of action is unclear. The purpose of this study was to use microarray analysis to determine whether ERbeta-selective compounds produce their anti-inflammatory effects by repressing transcription of proinflammatory genes. We identified 49 genes that were activated by TNF-alpha in human osteosarcoma U2OS cells expressing ERbeta. Estradiol treatment significantly reduced the activation by TNF-alpha on 18 genes via ERbeta or ERalpha. Most repressed genes were inflammatory genes, such as TNF-alpha, IL-6, and CSF2. Three ERbeta-selective compounds, ERB-041, WAY-202196, and WAY-214156, repressed the expression of these and other inflammatory genes. ERB-041 was the most ERbeta-selective compound, whereas WAY-202196 and WAY-214156 were the most potent. The ERbeta-selective compounds repressed inflammatory genes by recruiting the coactivator, SRC-2. ERB-041 also repressed cytokine genes in PBMCs, demonstrating that ERbeta-selective estrogens have anti-inflammatory properties in immune cells. Our study suggests that the anti-inflammatory effects of ERB-041 and other ERbeta-selective estrogens in animal models are due to transcriptional repression of proinflammatory genes. These compounds might represent a new class of drugs to treat inflammatory disorders. Keywords: estrogen receptor, gene regulation, TNF