Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

<p>Abstract</p> <p>Background</p> <p>Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH₃/B₆/F₁₀, originally subcloned from GH₃cells based on its ability to express high levels of the membrane estrogen receptor-α.</p> <p>Methods</p> <p>We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities.</p> <p>Results</p> <p>Four phytoestrogens (coumestrol, daidzein, genistein, and <it>trans</it>-resveratrol) were studied over wide concentration ranges. Except <it>trans</it>-resveratrol, all phytoestrogens increased GH₃/B₆/F₁₀cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for <it>trans</it>-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens.</p> <p>Conclusion</p> <p>Phytoestrogens can block physiological estrogen-induced tumor cell growth <it>in vitro </it>and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary.</p

Mutagenicity of aryl propylene and butylene oxides with Salmonella

10 aryl propylene oxides and 6 aryl butylene oxides were synthesized. Dose-mutagenicity relationships were studied for these compounds and for 1,2-epoxybutane, using both the preincubation and plate incorporation Ames tests with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined by concurrent testing at single doses with the plate incorporation assay in strain TA100. In both series of compounds, mutagenicity showed very weak correlation to chemical reactivity, molar volume and partition values. However, all compounds were mutagenic in at least one system with the propylene oxides being more mutagenic than the corresponding butylene oxide derivatives. The naphthyl derivatives in each series were the most mutagenic.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26518/1/0000056.pd

CONTAINER TECHNOLOGIES AS LOGISTICAL INFRASTRUCTURE: HOW MARIE KONDO, THE CONTAINER STORE, HOLLINGER BOXES, AND DOCKER SHAPE OUR WORLD

This dissertation is situated at the intersection of digital studies, critical information studies, and cultural studies—I argue that containers undergird the logistical infrastructures of modern capitalism and social life, and they shape the way we think. By understanding our world through this framework, we can apply the perspective to understand problems we face in memory institutions, cloud computing, the retail sector, the culture industry, and even in the ongoing global pandemic, COVID-19. The first chapter considers physical containers, with a focus on the ‘Hollinger box’ (an omnipresent cardboard storage box at memory institutions), which has a design history rooted in World War II and the US’s fight against fascism. The second chapter focuses on Docker, a digital container system, which accelerates containers in cloud computing—I present a protohistory of digital containerization in computing history and look to the role of speed to accelerate information and global capital. The third chapter locates its discussion at a retail site, The Container Store, which facilitates consumerism and the commodification of containment. The fourth chapter looks to Marie Kondo and her KonMari Method. Kondo’s ‘joy’ is rooted in consumer culture, individualism, and storage in containers; her ‘tidying festivals’ are celebrations of capitalism. By tracing the interconnected histories behind these container systems, the dissertation demonstrates how the logic of containerization becomes embedded in our memory institutions, digital technologies, retail systems, and consumer culture. Containers in our society are subsumed by preexisting systems in capitalism: logistics and consumerism, in particular. Container technologies play a central role in our logistical infrastructures: wielded properly, containers hold the power to help us resolve many of our most pressing problems, and they can help us to improve the way we allocate resources equitably, rather than the reverse. But containers do not afford us a quick fix—rather, they offer us insight and a framework to understand the world we live in. Containers, when understood as key to the logistical infrastructure that undergird modern life, offer us the tools to reorganize our world and build it into something better