Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.This research was funded by the Prostate Cancer Research Centre charity (registered UK charity no. 1156027), Grant Number AA1. A small financial contribution was also made through intra-mural funds from the Royal Veterinary College.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.016110

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Issues of Participation: A Framework for Choices and Compromises

This paper appears in the International Journal of Sociotechnology and Knowledge Development edited by Constance Kampf (Aarhus University, Denmark) and José Abdelnour-Nocera (University of West London, UK). Copyright 2014, IGI Global, www.igi-global.com. Posted by permission of the publisher.Members of the Participatory Design (PD) community often raise concerns about participation – participation in what, by whom, and for what purpose? To help determine and answer questions important to participatory practice, the author derived a framework of key issues of participation using literature from Participatory Design and related practices such as Participatory Action Research, Participatory Democracy and Participatory Development. The key issues are: values, representation, power relations, context, transformations, effectiveness, and sustainability. The author posits that giving attention to these issues when designing, conducting and reflecting on participation will improve participatory practices by making choices and compromises more explicit to those involved in the research as well as those who review the research results. The paper discusses how the author derived the framework and then uses the selected literature to explore each of the seven issues and how they can be addressed in participatory practice in general, and within PD more specifically

Understanding the Information Research Process of Experienced Online Information Researchers to Inform Development of a Scholars Portal

<b>Objective </b>- The main purpose of this study was to understand the information research process of experienced online information researchers in a variety of disciplines, gather their ideas for improvement and as part of this to validate a proposed research framework for use in future development of Ontario’s Scholars Portal.<br><b>Methods </b>- This was a qualitative research study in which sixty experienced online information researchers participated in face-to-face workshops that included a collaborative design component. The sessions were conducted and recorded by usability specialists who subsequently analyzed the data and identified patterns and themes.<br><b>Results</b> - Key themes included the similarities of the information research process across all disciplines, the impact of interdisciplinarity, the social aspect of research and opportunities for process improvement. There were many specific observations regarding current and ideal processes. Implications for portal development and further research included: supporting a common process while accommodating user-defined differences; supporting citation chaining practices with new opportunities for data linkage and granularity; enhancing keyword searching with various types of intervention; exploring trusted social networks; exploring new mental models for data manipulation while retaining traditional objects; improving citation and document management. <br><b>Conclusion</b> – The majority of researchers in the study had almost no routine in their information research processes, had developed few techniques to assist themselves and had very little awareness of the tools available to help them. There are many opportunities to aid researchers in the research process that can be explored when developing scholarly research portals. That development will be well guided by the framework ‘discover, gather, synthesize, create, share.

Danica Jojich : Armed to Be Allowed

The artist describes his image/object combinations as participatory, performative pieces which invite the viewer to re-examine homelessness, war, brutality and poverty. Black-and-white photographs of wearable objects being worn on the street are briefly introduced by Costantino. Biographical notes

Har Prakash Khalsa : The Divine Servant

Costantino's statement deals with the nostalgia, uneasiness and questioning that arise from Khalsa's photo/text works which pair silk scripture and personal snapshots, exploring the boundaries of identity and cultural difference. Artist's statement. Biographical notes

Valediction

Reflecting on the themes of death and decay, the authors consider the work of Clément, Claus and Neumark, in relation to recent critical theory on photography. Artist's statements. Biographical notes

Bed of Roses

Photographic works evolved from the Women Sexual Imagery Project are introduced by a text defining the challenges encountered during the workshop in the making of "alternative erotica". Statements by the seven participants. Brief biographical notes

Cigarette Smoking, Physical Activity, and Alcohol Consumption as Predictors of Cancer Incidence among Women at High Risk of Breast Cancer in the NSABP P-1 Trial

BACKGROUND: NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen. METHODS: From 1992–1997, 13,388 women with estimated 5-year breast cancer (BC) risk greater than 1.66% or a history of lobular carcinoma in situ (87% under age 65; 67% post-menopausal) were randomly assigned to tamoxifen versus placebo. Invasive BC, lung (LC), colon (CC), and endometrial cancers (EC) were analyzed with Cox regression. Predictors were baseline cigarette smoking, leisure-time physical activity, alcohol consumption, and established risk factors. RESULTS: At median 7 years follow-up, we observed 395, 66, 35, and 74 BC, LC, CC, and EC, respectively. Women who had smoked were at increased risk of BC (P=.007; hazard ratio (HR)=1.3 for 15–35 years smoking, HR=1.6 for ≥35 years), LC (P<.001; HR=3.9 for 15–35 years; HR=18.4 for ≥35 years), and CC (P<.001; HR=5.1 for ≥35 years) versus never-smokers. Low activity predicted increased BC risk only among women assigned to placebo (P=.021 activity main effect, P=.013 activity-treatment interaction; HR=1.4 for placebo group) and EC among all women (P=.026, HR=1.7). Moderate alcohol (>0–1 drink/day) was associated with decreased risk of CC (P=.019; HR=.35) versus no alcohol. There were no other significant associations between these behaviors and cancer risk. CONCLUSION: Among women with elevated risk of BC, smoking has an even greater impact on BC risk than observed in past studies in the general population. IMPACT: Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer