High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self-protection. We then used fluorescence-activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony-forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub-populations of cells demonstrating stem-cell-like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF-7. When isolated and compared to ALDHlowCD44low/- cells, ALDHhiCD44+CD24- (MDA-MB-231) and ALDHhiCD44+CD133+ (MDA-MB-468) cells demonstrated increased growth (P \u3c 0.05), colony formation (P \u3c 0.05), adhesion (P \u3c 0.001), migration (P \u3c 0.001) and invasion (P \u3c 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2 gamma receptor null mice, ALDHhiCD44+CD24- and ALDHhiCD44+CD133+ cells showed enhanced tumorigenicity and metastasis relative to ALDHlowCD44low/- cells (P \u3c 0.05). These novel results suggest that stem-like ALDHhiCD44+CD24- and ALDHhiCD44+CD133+ cells may be important mediators of breast cancer metastasis

Applying Phenomenography to Develop a Comprehensive Understanding of Ethics in Engineering Practice

This Work-in-Progress Research paper describes (1) the contemporary research space on ethics education in engineering; (2) our long-term research plan; (3) the theoretical underpinnings of Phase 1 of our research plan (phenomenography); and (4) the design and developmental process of a phenomenographic interview protocol to explore engineers' experiences with ethics. Ethical behavior is a complex phenomenon that is complicated by the institutional and cultural contexts in which it occurs. Engineers also have varied roles and often work in a myriad of capacities that influence their experiences with and understanding of ethics in practice. We are using phenomenography, a qualitative research approach, to explore and categorize the ways engineers experience and understand ethical engineering practice. Specifically, phenomenography will allow us to systematically investigate the range and complexity of ways that engineers experience ethics in professional practice in the health products industry. Phenomenographic data will be obtained through a specialized type of semi-structured interview. Here we introduce the design of our interview protocol and its four sections: Background, Experience, Conceptual, and Summative. We also describe our iterative process for framing questions throughout each section

Activation of p107 by Fibroblast Growth Factor, Which Is Essential for Chondrocyte Cell Cycle Exit, Is Mediated by the Protein Phosphatase 2A/B55α Holoenzyme

The phosphorylation state of pocket proteins during the cell cycle is determined at least in part by an equilibrium between inducible cyclin-dependent kinases (CDKs) and serine/threonine protein phosphatase 2A (PP2A). Two trimeric holoenzymes consisting of the core PP2A catalytic/scaffold dimer and either the B55α or PR70 regulatory subunit have been implicated in the activation of p107/p130 and pRB, respectively. While the phosphorylation state of p107 is very sensitive to forced changes of B55α levels in human cell lines, regulation of p107 in response to physiological modulation of PP2A/B55α has not been elucidated. Here we show that fibroblast growth factor 1 (FGF1), which induces maturation and cell cycle exit in chondrocytes, triggers rapid accumulation of p107-PP2A/B55α complexes coinciding with p107 dephosphorylation. Reciprocal solution-based mass spectrometric analysis identified the PP2A/B55α complex as a major component in p107 complexes, which also contain E2F/DPs, DREAM subunits, and/or cyclin/CDK complexes. Of note, p107 is one of the preferred partners of B55α, which also associates with pRB in RCS cells. FGF1-induced dephosphorylation of p107 results in its rapid accumulation in the nucleus and formation of larger complexes containing p107 and enhances its interaction with E2F4 and other p107 partners. Consistent with a key role of B55α in the rapid activation of p107 in chondrocytes, limited ectopic expression of B55α results in marked dephosphorylation of p107 while B55α knockdown results in hyperphosphorylation. More importantly, knockdown of B55α dramatically delays FGF1-induced dephosphorylation of p107 and slows down cell cycle exit. Moreover, dephosphorylation of p107 in response to FGF1 treatment results in early recruitment of p107 to the MYC promoter, an FGF1/E2F-regulated gene. Our results suggest a model in which FGF1 mediates rapid dephosphorylation and activation of p107 independently of the CDK activities that maintain p130 and pRB hyperphosphorylation for several hours after p107 dephosphorylation in maturing chondrocytes

The Grizzly, February 11, 1983

Bookstore Explains Pricing Policy • Scottish Scholarships Offered to Sophomores • Weekend Alcohol Policy: Campus is Dry • Ursinus Gets Bucks From Sears Roebuck • President\u27s Corner • Visser Fills Exhibits in Corson • Letters to the Editor: Professor Laments Social Conditions at UC; I.F.C. President Irate; President\u27s Response; Bitter About Policy • Varying Viewpoints • Stravinsky to End Winterfest • U.C. Flu Flattens Students • Reaganomics Forum • Key Shooting Aids Lady Hoopsters\u27 Record • Basketball Laments Second Half Loss • Swimmers Glide to Third Straight Victory • Grapplers Deemed Tough • Basketball: End of an Era?? • Swimmers Stroke for Two Wins • Gymnasts Win by 0.75https://digitalcommons.ursinus.edu/grizzlynews/1093/thumbnail.jp

Strokes of serendipity: community co-curation and engagement with digital heritage

This article explores the potential that community–led digital engagement with heritage holds for stimulating active citizenship through taking responsibility for shared cultural heritage and for fostering long-lasting relationships between local community heritage groups and national museums. Through the lens of a pilot project titled Science Museum: Community-in- Residence, we discovered that — despite working with community groups that were already loyal to and enjoyed existing working ties with the Science Museum in London, U.K — this undertaking proved challenging owing to a range of structural and logistical issues even before the application of digital devices and tools had been considered. These challenges notwithstanding, the pilot found that the creation of time and space for face-to-face dialogue and interactions between the Science Museum and the participating community heritage groups helped to establish the parameters within which digital co-curation can effectively occur. This, in turn, informed the development of a digital prototype with huge potential to enable remote, virtual connectivity to, and interactivity with, conversations about shared heritage. The ultimate goal was two-fold: (a) to help facilitate collaborative sense-making of our shared past, and (b) to aid the building of sustainable institutional and community/public working ties around emerging affinities, agendas and research questions in relation to public history and heritage

Deciphering ocean carbon in a changing world

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 113 (2016): 3143-3151, doi:10.1073/pnas.1514645113.Dissolved organic matter (DOM) in the oceans is one of the largest pools of reduced carbon on Earth, comparable in size to the atmospheric CO2 reservoir. A vast number of compounds are present in DOM and they play important roles in all major element cycles, contribute to the storage of atmospheric CO2 in the ocean, support marine ecosystems, and facilitate interactions between organisms. At the heart of the DOM cycle lie molecular-level relationships between the individual compounds in DOM and the members of the ocean microbiome that produce and consume them. In the past, these connections have eluded clear definition because of the sheer numerical complexity of both DOM molecules and microorganisms. Emerging tools in analytical chemistry, microbiology and informatics are breaking down the barriers to a fuller appreciation of these connections. Here we highlight questions being addressed using recent methodological and technological developments in those fields and consider how these advances are transforming our understanding of some of the most important reactions of the marine carbon cycle.Support was provided by National Science Foundation grants OCE1356010, OCE1154320, and OCE1356890, and Gordon and Betty Moore Foundation Grant #3304

Older adults’ preferences for colorectal cancer-screening test attributes and test choice

BackgroundUnderstanding which attributes of colorectal cancer (CRC) screening tests drive older adults’ test preferences and choices may help improve decision making surrounding CRC screening in older adults.Materials and methodsTo explore older adults’ preferences for CRC-screening test attributes and screening tests, we conducted a survey with a discrete choice experiment (DCE), a directly selected preferred attribute question, and an unlabeled screening test-choice question in 116 cognitively intact adults aged 70–90 years, without a history of CRC or inflammatory bowel disease. Each participant answered ten discrete choice questions presenting two hypothetical tests comprised of four attributes: testing procedure, mortality reduction, test frequency, and complications. DCE responses were used to estimate each participant’s most important attribute and to simulate their preferred test among three existing CRC-screening tests. For each individual, we compared the DCE-derived attributes to directly selected attributes, and the DCE-derived preferred test to a directly selected unlabeled test.ResultsOlder adults do not overwhelmingly value any one CRC-screening test attribute or prefer one type of CRC-screening test over other tests. However, small absolute DCE-derived preferences for the testing procedure attribute and for sigmoidoscopy-equivalent screening tests were revealed. Neither general health, functional, nor cognitive health status were associated with either an individual’s most important attribute or most preferred test choice. The DCE-derived most important attribute was associated with each participant’s directly selected unlabeled test choice.ConclusionOlder adults’ preferences for CRC-screening tests are not easily predicted. Medical providers should actively explore older adults’ preferences for CRC screening, so that they can order a screening test that is concordant with their patients’ values. Effective interventions are needed to support complex decision making surrounding CRC screening in older adults

Climate change and water in the UK: past changes and future prospects

Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they mak

Changes in the arabinoxylan fraction of wheat grain during 1 alcohol production

Laboratory produced DDGS samples were compared with commercial samples from a distillery and a biofuel plant. Changes in structure, solubility and content of arabinoxylan (AX) was determined. The distillation process results in a relative increase of AX content compared to the starting material. The heating and drying processes involved in the production of DDGS lead to an increased solubility and viscosity of water-extractable AX. Production of DDGS results in structural changes to the AX. There is a decrease in 2-and 3-linked arabinose oligosaccharides, that contributes to around a 50% reduction in arabinosylation in DDGS compared with the starting grains. The current study shows that laboratory-scale DDGS provide an accurate representation of the commercial scale and that the AX composition of DDGS is consistently uniform irrespective of starting material. The uniformity of DDGS and thin stillage makes them a good potential source of AX for production of prebiotics or other novel products