Membrane fluidity and epidermal growth factor receptor function in breast cancer

The epidermal growth factor receptor (EGFR) has been implicated in the growth and development of a number of human cancers including breast cancer. The activity and expression of membrane associated proteins such as the EGFR may be modulated by the physical state of the membrane. Activation of the EGFR depends on the lateral diffusion and dimerisation of receptor monomers. Changes in membrane fluidity may therefore affect activation of the EGFR and hence growth signalling via this receptor. Using the technique of fluorescence recovery after photobleaching, the lateral diffusion of number of fluorescent lipid probes was studied in three breast cancer cell lines (MCF-7, MDA-MB-231 and MCF-7AdrR). The antiestrogen drug tamoxifen which is widely used in the treatment of breast cancer, was demonstrated to decrease membrane fluidity in breast cancer cells e.g. in MCF-7 cells a 24 hour incubation with l0-6M tamoxifen decreased the lateral diffusion coefficient of the AF18 probe from 203 xl0-10cm2/s to 15.4 xl0-10cm2/s. Tamoxifen treatment had a general effect on membrane fluidity which was observed using different lipid probes and was not dependent on the estrogen receptor status of the cell line. Tamoxifen's ability to decrease membrane fluidity may be due to its ability to adopt a conformation which resembles the steroid nucleus. The steroids cholesterol, 17?-estradiol and the steroidal antiestrogen ICIl82,780 all had a similar effect on membrane fluidity. Tamoxifen has previously been reported to have several actions unrelated to inhibition of estrogen action. Tamoxifen can inhibit the growth of cells in the complete absence of estrogens and also inhibit cells which do not express the estrogen receptor. Tamoxifen can inhibit EGF-stimulated growth of MCF-7 breast cancer cells by a mechanism distinct from induction of TGF? production. Tamoxifen had no effect on the cell surface expression or affinity of the EGFR and it did not inhibit the EGFR tyrosine kinase activity in isolated cell membranes. However, in intact cells tamoxifen treatment inhibited EGFR autophosphorylation. This effect could be due to stabilisation of the membrane by tamoxifen and consequent reduction in the lateral diffusion of the EGF receptor, reducing dimerisation and autophosphorylation of the receptor. This would reduce growth stimulation initiated via the EGFR. Tamoxifen can be demonstrated to reduce EGFR mobility in A431 cells. These cells have elevated levels of EGFR which allow a sufficient level of signal for FRAP measurements of receptor mobility. It is therefore possible that tamoxifen's membrane effects contribute to its anticancer action by interfering with EGFR function. The rate of internalisation of the EGFR was not altered by tamoxifen treatment which suggests that EGFR lateral diffusion is not a rate-limiting factor in receptor internalisation. Tamoxifen treatment also had no effect on the adriamycin sensitivity of the drug resistant cell line MCF-7AdrR

Determining geological controls on nutrient availability at different depths in the soils of the Pelee Island Winery

Terroir describes a sense of place that can give a unique flavour to wines grown in different environments. We explored the role of soil in the terroir at Canada’s most southern vineyard, Pelee Island Winery. This study examined the abundance of major nutrients, trace and rare earth elements of minerals and plant extractable nutrients from 19 soils across the vineyard to a depth of 2 m. We found that bedrock does not influence the element content of Pelee Island soils, the parent materials of the soils are tills and there are geochemical, mineralogical and grain size differences between the two soil types on the island. Nutrient distribution throughout the soil profile was controlled by soil weathering with organic matter concentrating most nutrients in surface soils. Agricultural and anthropogenic influences had minimal effects on soil nutrient concentrations

Invisible design: exploring insights and ideas through ambiguous film scenarios

Invisible Design is a technique for generating insights and ideas with workshop participants in the early stages of concept development. It involves the creation of ambiguous films in which characters discuss a technology that is not directly shown. The technique builds on previous work in HCI on scenarios, persona, theatre, film and ambiguity. The Invisible Design approach is illustrated with three examples from unrelated projects; Biometric Daemon, Panini and Smart Money. The paper presents a qualitative analysis of data from a series of workshops where these Invisible Designs were discussed. The analysis outlines responses to the films in terms of; existing problems, concerns with imagined technologies and design speculation. It is argued that Invisible Design can help to create a space for critical and creative dialogue during participatory concept development

Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention

Equine protozoal myeloencephalitis (EPM) remains an important neurologic disease of horses. There are no pathognomonic clinical signs for the disease. Affected horses can have focal or multifocal central nervous system (CNS) disease. EPM can be difficult to diagnose antemortem. It is caused by either of 2 parasites, Sarcocystis neurona and Neospora hughesi, with much less known about N. hughesi. Although risk factors such as transport stress and breed and age correlations have been identified, biologic factors such as genetic predispositions of individual animals, and parasite-specific factors such as strain differences in virulence, remain largely undetermined. This consensus statement update presents current published knowledge of the parasite biology, host immune response, disease pathogenesis, epidemiology, and risk factors. Importantly, the statement provides recommendations for EPM diagnosis, treatment, and prevention

The Lantern, 2010-2011

• The Graterford Department of Corrections • Visiting Room: Lewis Considers the Space & Time Continuum • String • The Tale of Lad Wadley • The Devout • One Moment in the Garden • Water, Focused and Tumbling • Bomber • Another • I Walked Home • Perhe • I Describe the Last Time My Parents Had Sex • Butterflies • Ship Without Fools • The Interview • Cyane • An Imaginary Portrait of Stella as a Young Girl • At the Farm Market in Early Autumn • Victor Jorgenson\u27s Photograph of the V-J Day Kiss • Lightning • The Citadel • Whenever You Come Home From School • It Came in a Dream • What I Know About Fission • Please Don\u27t Fire Me for Saying Such Things • Femina Irata • Thank You For Shopping • Sunday, November 27th • An Introduction to The Lifestyle • Laid-Off Perception • Good-Night, Sweet Prince • Requiem for a Marriage • Gertrude\u27s Book • Passing • Elk Run II • Shady Tides • A Quiet House • Tell Him. A Manual • Silence • Google This • The Dinner Table Dance • The Inevitable Extinction of Filing Cabinets • Chateau d\u27If • Man Smoking in Charcoal • Inside Auschwitz • Bark Glow • Anticipation • Look Up • Major News Networks • Others Wage War • Insert Bible Verse Here • The Empress • Candy Castle • Venice, Italy • Quebec • Bhutanese Child • Jumper • Pomegranates • Cover Image: Octopus Hathttps://digitalcommons.ursinus.edu/lantern/1176/thumbnail.jp

The Lantern, 2011-2012

• Frangipani • A Shadow • Dear Anne, In this Place, Stringbean Girls • Back to a Dandelion • How to Plant a Room • Swimming Pool Poem 30 • The Naming of Daughters • Berman Museum Photographs • Truth or Dare • The Song of Remembrance, L\u27vov, Poland, 1940 • Headlights • Prayer of Thanks • Numbers Game • Pediment • Home Sick • Lust • Sand Lining Instructions • A-A-Ask a Question • Flash Cards • Columbus Day • Mr. Yoest Gives His Report to the Police Officers on Wednesday Night • Gender Trouble • The Internet Connection at Ursinus College • Assuming You\u27ll Still be Here • 10/28/11, Third Poem • October • Actions that Affirm and Confirm Us as a Community • Why I Hate The Lantern • Confessions of an Ex-Vegetarian • Run • Lunch at Caltort • Schemers • You Will Make Beautiful Babies in America • The Black Dirt Region • Il Travatore • Ghost Story • Blue Eyes and Sunny Skies • A Little Sincerity • The Bookstore • The Opposite of Serendipity • The Human Doll • Evil Deeds • Francesca • Sunday Morning • Jersey Aesthetic • Jump! • Behind Reimert • Seaweed in New Zealand • Tombee de L\u27elegance • The Window • Esperando • Rainbow to the Heavens • Encased • In Springtime • A Fiesolan Monk\u27s Room • Inside a Bone • Neon Indian • Moments of Clarity • OneFeral: A Feral Self-Portrait • Cover Image: The Conquerorhttps://digitalcommons.ursinus.edu/lantern/1177/thumbnail.jp

Causes of decoupling between larval supply and settlement and consequences for understanding recruitment and population connectivity

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Experimental Marine Biology and Ecology 392 (2010): 9-21, doi:10.1016/j.jembe.2010.04.008.Marine broadcast spawners have two-phase life cycles, with pelagic larvae and benthic adults. Larval supply and settlement link these two phases and are crucial for the persistence of marine populations. Mainly due to the complexity in sampling larval supply accurately, many researchers use settlement as a proxy for larval supply. Larval supply is a constraining variable for settlement because, without larval supply, there is no settlement. Larval supply and settlement may not be well correlated, however, and settlement may not consistently estimate larval supply. This paper explores the argument that larval supply (i.e., larval abundance near settlement sites) may not relate linearly to settlement. We review the relationship between larval supply and settlement, from estimates and biases in larval supply sampling, to non-behavioral and behavioral components, including small-scale hydrodynamics, competency, gregarious behavior, intensification of settlement, lunar periodicity, predation and cannibalism. Physical and structural processes coupled with behavior, such as small-scale hydrodynamics and intensification of settlement, sometimes result in under- or overestimation of larval supply, where it is predicted from a linear relationship with settlement. Although settlement is a function of larval supply, spatial and temporal processes interact with larval behavior to distort the relationship between larval supply and settlement, and when these distortions act consistently in time and space, they cause biased estimates of larval supply from settlement data. Most of the examples discussed here suggest that behavior is the main source of the decoupling between larval supply and settlement because larval behavior affects the vertical distribution of larvae, the response of larvae to hydrodynamics, intensification of settlement, gregariousness, predation and cannibalism. Thus, larval behavior seems to limit broad generalizations on the regulation of settlement by larval supply. Knowledge of the relationship is further hindered by the lack of a well founded theoretical relationship between the two variables. The larval supply- settlement transition may have strong general consequences for population connectivity, since larval supply is a result of larval transport, and settlement constrains recruitment. Thus, measuring larval supply and settlement effectively allows more accurate quantification and understanding of larval transport, recruitment and population connectivity.JP would like to thank WHOI Ocean Life Institute for partial funding. FP’s contribution is based upon research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation

Co-designing Cards on Social Issues for Creating Educational Games

This paper presents a participatory methodology to design cards on social issues with the purpose to democratise knowledge among co-designers on the learning content of educational games. Situated on the topic of everyday sexism, the methodology has been developed through an iterative process involving two collaborative workshops, two iterations of card design and a feedback survey. Extracting findings from the workshops and the feedback gathered on the co- designed cards, this paper presents insights that could be used to inform similar studies using cards to inspire and foster reflection on social issues

Transcriptomic Analysis of Toxoplasma Development Reveals Many Novel Functions and Structures Specific to Sporozoites and Oocysts

Sexual reproduction of Toxoplasma gondii occurs exclusively within enterocytes of the definitive felid host. The resulting immature oocysts are excreted into the environment during defecation, where in the days following, they undergo a complex developmental process. Within each oocyst, this culminates in the generation of two sporocysts, each containing 4 sporozoites. A single felid host is capable of shedding millions of oocysts, which can survive for years in the environment, are resistant to most methods of microbial inactivation during water-treatment and are capable of producing infection in warm-blooded hosts at doses as low as 1–10 ingested oocysts. Despite its extremely interesting developmental biology and crucial role in initiating an infection, almost nothing is known about the oocyst stage beyond morphological descriptions. Here, we present a complete transcriptomic analysis of the oocyst from beginning to end of its development. In addition, and to identify genes whose expression is unique to this developmental form, we compared the transcriptomes of developing oocysts with those of in vitro-derived tachyzoites and in vivo-derived bradyzoites. Our results reveal many genes whose expression is specifically up- or down-regulated in different developmental stages, including many genes that are likely critical to oocyst development, wall formation, resistance to environmental destruction and sporozoite infectivity. Of special note is the up-regulation of genes that appear “off” in tachyzoites and bradyzoites but that encode homologues of proteins known to serve key functions in those asexual stages, including a novel pairing of sporozoite-specific paralogues of AMA1 and RON2, two proteins that have recently been shown to form a crucial bridge during tachyzoite invasion of host cells. This work provides the first in-depth insight into the development and functioning of one of the most important but least studied stages in the Toxoplasma life cycle