"Spinning Their Wheels "-Influences That Shape How Nurse Educators Teach Social Justice.

Despite institutional claims that social justice is a core professional nursing value, efforts to fulfill this claim remain uneven. The purpose of this study was to examine the circumstances that shape nursing educators' approaches to social justice. In-depth semi-structured interviews with 28 educators teaching theory courses in baccalaureate nursing programs shed light upon the influences that shape how educators integrate social justice. These include formative experiences, institutional factors, and curricular opportunities. Formative experiences include upbringing, educational background, and preparation to teach. Institutional factors consist of the type of institution, geographic location, and the specter of retention, promotion, and tenure. Finally, curricular opportunities and fit include the positioning of Community Health Nursing, fragmentation and tension between "content and context," and the "driving force" of the National Council Licensure Examination for Registered Nurses (NCLEX). Findings indicate that the capacity to uphold the value of social justice is shaped by experiences across the lifespan, institutional policies, and practices related to faculty hiring, development, career advancement, as well as curricular vision. This study calls for a concerted effort to enact social justice nursing education.

"Social justice is a dream": Tensions and contradictions in nursing education.

OBJECTIVE: The purpose of this study was to explore nurse educators' conceptualizations of social justice in theory courses. The findings contextualize the role of nurse educators in promoting social justice among future health care providers and the relevance of their perspectives on social justice. DESIGN: This descriptive qualitative study was completed utilizing constructivist grounded theory methods. SAMPLE AND MEASUREMENTS: I interviewed 28 nurse educators teaching theory courses in Baccalaureate nursing programs on the West coast of the United States. Initial and focused codes were constructed from interview transcripts to understand and contextualize statements about social justice. RESULTS: Participants' conceptualizations of social justice include equity, equality, self-awareness, withholding judgment, and taking action. CONCLUSIONS: Notable differences emerged along racial lines and, less so, in relation to educational background and nursing specialty. This study highlights areas of concern with respect to how nurse educators enact the claim that social justice is a core professional nursing value. The findings call attention to tensions and contradictions as individuals navigate the landscape of nursing with limited structural and institutional effort.

Photoisomerization of ß-Ionone Protonated Schiff Base in the Gas Phase.

The photoisomerization of ß-ionone protonated Schiff base (BIPSB) is investigated in the gas phase by irradiating mobility-selected ions in a tandem ion mobility spectrometer with tunable radiation. Four distinguishable isomers are produced by electrospray ionization whose structures are deduced from their collision cross sections and photoisomerization behavior along with density functional theory calculations. They include two geometric isomers of BIPSB with trans or cis configurations about the polyene chain's terminal C═N double bond, a bicyclic structure formed through electrocyclization of the polyene chain, and a Z-retro-γ-ionone isomer. Although trans-BIPSB and 9-cis-BIPSB have similar photoisomerization action spectra, with a maximum response at 375 nm, they photoconvert to different isomers. The trans-BIPSB isomer transforms to the bicyclic form upon exposure to light over the 320-400 nm range, whereas the cis-BIPSB isomer is prevented by steric hindrance from forming the bicyclic BIPSB isomer following irradiation and is proposed instead to form the 7,9-di-cis isomer. Neither the bicyclic isomer nor the Z-retro-γ-ionone isomer respond strongly to near-UV light.

Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines.

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome-wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours' biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription-quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes.

N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF.

A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be switched in favour of ERCC1-XPF over FEN-1. Further exploration of the structure-activity relationships around this chemotype gave sub-micromolar inhibitors with >10-fold selectivity for ERCC1-XPF over FEN-1.

Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF.

Catechol-based inhibitors of ERCC1-XPF endonuclease activity were identified from a high-throughput screen. Exploration of the structure-activity relationships within this series yielded compound 13, which displayed an ERCC1-XPF IC50 of 0.6 µM, high selectivity against FEN-1 and DNase I and activity in nucleotide excision repair, cisplatin enhancement and γH2AX assays in A375 melanoma cells. Screening of fragments as potential alternatives to the catechol group revealed that 3-hydroxypyridones are able to inhibit ERCC1-XPF with high ligand efficiency, and elaboration of the hit gave compounds 36 and 37 which showed promising ERCC1-XPF IC50 values of <10 µM.

Inhibition of the ERCC1-XPF structure-specific endonuclease to overcome cancer chemoresistance.

ERCC1-XPF is a structure-specific endonuclease that is required for the repair of DNA lesions, generated by the widely used platinum-containing cancer chemotherapeutics such as cisplatin, through the Nucleotide Excision Repair and Interstrand Crosslink Repair pathways. Based on mouse xenograft experiments, where ERCC1-deficient melanomas were cured by cisplatin therapy, we proposed that inhibition of ERCC1-XPF could enhance the effectiveness of platinum-based chemotherapy. Here we report the identification and properties of inhibitors against two key targets on ERCC1-XPF. By targeting the ERCC1-XPF interaction domain we proposed that inhibition would disrupt the ERCC1-XPF heterodimer resulting in destabilisation of both proteins. Using in silico screening, we identified an inhibitor that bound to ERCC1-XPF in a biophysical assay, reduced the level of ERCC1-XPF complexes in ovarian cancer cells, inhibited Nucleotide Excision Repair and sensitised melanoma cells to cisplatin. We also utilised high throughput and in silico screening to identify the first reported inhibitors of the other key target, the XPF endonuclease domain. We demonstrate that two of these compounds display specificity in vitro for ERCC1-XPF over two other endonucleases, bind to ERCC1-XPF, inhibit Nucleotide Excision Repair in two independent assays and specifically sensitise Nucleotide Excision Repair-proficient, but not Nucleotide Excision Repair-deficient human and mouse cells to cisplatin.