The Role of E2F Transcription Factors in Oncogene Mediated Mammary Tumorigenesis

The Myc and Neu oncogenes are commonly amplified in breast cancer, and in order to determine their roles, one must study the pathways they regulate. It has been found that there may be a cross-regulatory relationship between Myc and Neu through the action of E2F transcription factors. Establishing and understanding any potential link between the Myc and Neu oncogenes would enhance our understanding of gene regulatory pathways in breast cancer, and possibly have clinical implications. Based largely on in-vitro studies, Myc had been previously suggested to act through a select number of E2F family members. Similarly, studies have also linked Neu to the action of the E2F pathway. In order to study the relevance of E2F transcription factors in these two pathways, I examined mammary tumor formation initiated by either the Myc and Neu oncogenes in mice deficient for the E2F1, E2F2, or E2F3 genes. Because there exists a high degree of functional redundancy, combinations of the E2Fs were also deleted. Development of glands deficient in the E2Fs as well as tumor start dates were examined in order to determine the contributions made by the specific E2Fs. It was found that E2F3 did not play a significant role in Myc-mediated tumorigenesis, but it did play a critical role in Neu-mediated tumorigenesis. E2Fs 1 and 2 had varying roles of importance between the two pathways, and even when mice were deficient for multiple E2Fs, tumorigenesis was able to occur. The data implies that the Rb-E2F pathway is only mildly involved in Myc-mediated mammary tumorigenesis, but that this pathway is more critical for Neu mediated tumorigenesis. This suggests that Myc most likely acts through several additional regulatory pathways, and Neu is dependent on the Cyclin D1-Rb E2F pathway.Mayers Summer Research Scholarship 2006Undergraduate Research Scholarship 2006-200

Patient's perspectives of non-compliance with medication and treatment regimes: A qualitative analysis

The importance of compliance as a concept among health care workers is reflected in the amount of research conducted relating to this topic. Various data base programmes such as Medline has revealed 9,718 articles on compliance, which includes 178 on medication and treatment compliance, all written within the last 5 years (1990-1995). The majority of research in this area has focussed on the subject of non-compliance from the health professionals' viewpoint, with few studies examining patients' perspectives ofnon-compliance. Within the authors' area of work (community nursing), non-compliance with medication and treatment regimes among patients seems to be a recurring problem. Personal experience indicates that little understanding of patients' views on compliance exists among the community health workers, doctors and nurses. Based on these shortcomings, and lack of reliable literature to satisfy the researchers' curiosity, the author has embarked on this particular research study. The aim of this study is to ascertain the reasons why some patients undermine their physicians' recommendations and do not follow the suggested medication or treatment regimes. The effects of non-compliancy by patients has ramifications not only on the health budget, but also on the patient-doctor relationship. From this study it is hoped that the important issues which patients percieve as influencing their decisions to 'non-comply' will be identified, in order that health professionals can effectively reevaluate their current practices in prescibing medication and treatment regimes

OBJECTIVE AND SUBJECTIVE KNOWLEDGE: IMPACTS ON CONSUMER DEMAND FOR GENETICALLY MODIFIED FOODS IN THE UNITED STATES AND THE EUROPEAN UNION

In the growing body of literature on consumer acceptance of genetically modified (GM) foods, there are significant differences on the impact of knowledge on acceptance of GM foods. One potential explanation is the manner in which knowledge is measured. The goal of this study is to differentiate and examine the impact of both subjective and objective knowledge related to acceptance of genetically modified foods. Data from surveys collected in the United States, England, and France is used.Research and Development/Tech Change/Emerging Technologies,

Nitrogen Heterocycles Form Peptide Nucleic Acid Precursors in Complex Prebiotic Mixtures

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth

Dissonance for Dissidents Choral Concert

https://dc.ewu.edu/music_performances/1693/thumbnail.jp

Optimal strategies for gravitational wave stochastic background searches in pulsar timing data

A low frequency stochastic background of gravitational waves may be detected by pulsar timing experiments in the next five to ten years. Using methods developed to analyze interferometric gravitational wave data, in this paper we lay out the optimal techniques to detect a background of gravitational waves using a pulsar timing array. We show that for pulsar distances and gravitational wave frequencies typical of pulsar timing experiments, neglecting the effect of the metric perturbation at the pulsar does not result in a significant deviation from optimality. We discuss methods for setting upper limits using the optimal statistic, show how to construct skymaps using the pulsar timing array, and consider several issues associated with realistic analysis of pulsar timing data.Comment: 20 pages, 6 figures. Added figure with sky sensitivity for Parkes Pulsar Timing Array, included dipole overlap reduction function and derivation in appendix, extended likelihood discussio

EGFR associated expression profiles vary with breast tumor subtype

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors.</p> <p>Results</p> <p><it>In vitro</it>, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed <it>in vitro</it>, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident <it>in vivo</it>, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors.</p> <p>Conclusion</p> <p>These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. <it>In vivo</it>, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.</p

Experimental nitrogen addition alters structure and function of a boreal poor fen: Implications for critical loads

Bogs and fens cover 6 and 21%, respectively, of the 140,329 km2 Oil Sands Administrative Area in northern Alberta. Regional background atmospheric N deposition is low (b2 kg N ha−1 yr−1 ), but oil sands development has led to increasing N deposition (as high as 17 kg N ha−1 yr−1 ). To examine responses to N deposition, over five years, we experimentally applied N (as NH4NO3) to a poor fen near Mariana Lake, Alberta, unaffected by oil sands activities, at rates of 0, 5, 10, 15, 20, and 25 kg N ha−1 yr−1 , plus controls (no water or N addition). At Mariana Lake Poor Fen (MLPF), increasing N addition: 1) progressively inhibited N2-fixation; 2) had no effect on net primary production (NPP) of Sphagnum fuscum or S. angustifolium, while stimulating S. magellanicum NPP; 3) led to decreased abundance of S. fuscum and increased abundance of S. angustifolium, S. magellanicum, Andromeda polifolia, Vaccinium oxycoccos, and of vascular plants in general; 4) led to an increase in stem N concentrations in S. angustifolium and S. magellanicum, and an increase in leaf N concentrations in Chamaedaphne calyculata, Andromeda polifolia, and Vaccinium oxycoccos; 5) stimulated root biomass and production;6) stimulated decomposition of cellulose, but not of Sphagnum or vascular plant litter; and 7) had no or minimal effects on net N mineralization in surface peat, NH4 +-N, NO3 −-N or DON concentrations in surface porewater, or peat microbial composition. Increasing N addition led to a switch from new N inputs being taken up primarily by Sphagnum to being taken up primarily by shrubs. MLPF responses to increasing N addition did not exhibit threshold triggers, but rather began as soon as N additions increased. Considering all responses to N addition, we recommend a critical load for poor fens in Alberta of 3 kg N ha−1 yr−1

Transformational school leadership as a key factor for teachers’ job attitudes during their first year in the profession

Teacher attrition is a global concern that is particularly prevalent among beginning teachers. Teachers' intrinsic motivation to teach, affective organisational commitment and job satisfaction are considered job attitudes that stop them from dropping out of the profession. This study explores the interplay between factors at the school level (i.e. transformational leadership of the principal, professional collegial support) and the teacher level (i.e. self-efficacy) influencing these job attitudes. A sample of 292 first-year primary-school teachers participated. The results of the path analysis demonstrated that transformational leadership of the principal is directly related to teachers' job attitudes in a positive way. Moreover, transformational leadership of the principal is also indirectly related to these attitudes, via both professional collegial support and teachers' self-efficacy. Implications for the supportive role of the principal in the teachers' first year in the profession are discussed