HDAC6 and Ubp-M BUZ domains recognize specific C-terminal sequences of proteins.

The BUZ/Znf-UBP domain is a protein module found in the cytoplasmic deacetylase HDAC6, E3 ubiquitin ligase BRAP2/IMP, and a subfamily of ubiquitin-specific proteases. Although several BUZ domains have been shown to bind ubiquitin with high affinity by recognizing its C-terminal sequence (RLRGG-COOH), it is currently unknown whether the interaction is sequence-specific or whether the BUZ domains are capable of binding to proteins other than ubiquitin. In this work, the BUZ domains of HDAC6 and Ubp-M were subjected to screening against a one-bead-one-compound (OBOC) peptide library that exhibited random peptide sequences with free C-termini. Sequence analysis of the selected binding peptides as well as alanine scanning studies revealed that the BUZ domains require a C-terminal Gly-Gly motif for binding. At the more N-terminal positions, the two BUZ domains have distinct sequence specificities, allowing them to bind to different peptides and/or proteins. A database search of the human proteome on the basis of the BUZ domain specificities identified 11 and 24 potential partner proteins for Ubp-M and HDAC6 BUZ domains, respectively. Peptides corresponding to the C-terminal sequences of four of the predicted binding partners (FBXO11, histone H4, PTOV1, and FAT10) were synthesized and tested for binding to the BUZ domains by fluorescence polarization. All four peptides bound to the HDAC6 BUZ domain with low micromolar K(D) values and less tightly to the Ubp-M BUZ domain. Finally, in vitro pull-down assays showed that the Ubp-M BUZ domain was capable of binding to the histone H3-histone H4 tetramer protein complex. Our results suggest that BUZ domains are sequence-specific protein-binding modules, with each BUZ domain potentially binding to a different subset of proteins.

Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.

BACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. METHODS: We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR. RESULTS: Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p=9.2x10(-4)) and triglycerides (p=1.3x10(-3)) and the triglyceride:HDL cholesterol ratio (p=2.7x10(-4)). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women<45 years old (p=0.002). CONCLUSIONS: Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

Gene expression signatures of radiation response are specific, durable and accurate in mice and humans.

BACKGROUND: Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. METHODS AND FINDINGS: We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively. CONCLUSIONS: We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.

The professionalism disconnect: do entering residents identify yet participate in unprofessional behaviors?

BACKGROUND: Professionalism has been an important tenet of medical education, yet defining it is a challenge. Perceptions of professional behavior may vary by individual, medical specialty, demographic group and institution. Understanding these differences should help institutions better clarify professionalism expectations and provide standards with which to evaluate resident behavior. METHODS: Duke University Hospital and Vidant Medical Center/East Carolina University surveyed entering PGY1 residents. Residents were queried on two issues: their perception of the professionalism of 46 specific behaviors related to training and patient care; and their own participation in those specified behaviors. The study reports data analyses for gender and institution based upon survey results in 2009 and 2010. The study received approval by the Institutional Review Boards of both institutions. RESULTS: 76% (375) of 495 PGY1 residents surveyed in 2009 and 2010 responded. A majority of responders rated all 46 specified behaviors as unprofessional, and a majority had either observed or participated in each behavior. For all 46 behaviors, a greater percentage of women rated the behaviors as unprofessional. Men were more likely than women to have participated in behaviors. There were several significant differences in both the perceptions of specified behaviors and in self-reported observation of and/or involvement in those behaviors between institutions.Respondents indicated the most important professionalism issues relevant to medical practice include: respect for colleagues/patients, relationships with pharmaceutical companies, balancing home/work life, and admitting mistakes. They reported that professionalism can best be assessed by peers, patients, observation of non-medical work and timeliness/detail of paperwork. CONCLUSION: Defining professionalism in measurable terms is a challenge yet critical in order for it to be taught and assessed. Recognition of the differences by gender and institution should allow for tailored teaching and assessment of professionalism so that it is most meaningful. A shared understanding of what constitutes professional behavior is an important first step.

Achieving Gender Equality

This essay asserts that both men and women must work together to break the ubiquitous glass ceiling in the sciences.

Revising Justice: Punitory Thought and Action in the Work of Atwood, Jordan, and Oates

*Designated as an exemplary master's project for 2015-16*

Tennyson and youth

This paper will examine the prominence of Alfred Tennyson's work in several textual accounts of youth penned between 1892 and the present day, by writers including T. S. Eliot, Virgina Woolf, Joseph Conrad, James Joyce, Kingsley Amis, J. M. Coetzee, William Faulkner and Andrew Motion. The young Woolf broke in her new pens by copying out Tennyson's 'Tithonus'; Eliot had a taste for Tennyson's 'martial and sanguinary poetry; as a young man. Kingsley Amis was singular among his contemporaries precisely because he admired the work of a poet considered outdated, and a reference for Modernist verse over that of Tennyson is seen as a sign of sophistication (however ironically presented) in the writings of people as diverse as Auden, Motion and Coetzee. [From the Author]

On "fitting in": the effects of social context and gender on big 5 trait expression.

[This is a summary of an Oral Presentation] The study explored the expression of Big 5 personality traits in three different social contexts (with parents friends and work colleagues) to test the prediction that personality is socially variable due to the motivation to ‘fit in’. The questionnaire-based method produced results that support this hypothesis; all Big 5 traits were significantly variable across contexts with Conscientiousness the least variable and Extraversion possessiveness. The results indicated that females reported being more distressed than males and older respondents reported being less distressed then younger respondents. The findings from this study contribute to the literature on online infidelity in terms of understanding differences in the way it is perceived.

'Bowing from the heart': an investigation into discourses of professionalism and the work of caring for students in further education

Since their incorporation in 1993, further education (FE) colleges in England have been responsible for their own staffing and, faced with funding constraints as well as recruitment and retention targets, some have introduced a new category of staff referred to here as 'learning support workers' (LSWs). Though their employment conditions and specific duties vary considerably, LSWs' work often includes providing individual care for students. In this small-scale study, using semi-structured interviews, the perceptions of some teachers and LSWs about the nature of their relationships with each other and with students are investigated. The study is set broadly in the context of debates about the impact of public sector reform on FE colleges and teachers. A discourse analysis approach is adopted in discussion of the data. The authors conclude that although they are differently positioned in relation to traditional discourses of professionalism, both teachers and LSWs are perceived to be carrying out what Hochschild termed 'emotional labour'. The contradictory nature of emotional labour is also highlighted. Some of the implications of employing a new group of workers in FE are discussed.

Validation of the detection of Pseudo-nitzschia spp. using specific RNA probes tested in a microarray format: Calibration of signal based on variability of RNA content with environmental conditions.

Harmful algal blooms (HAB) occur worldwide and cause health problems and economic damage to fisheries and tourism. Monitoring for toxic algae is therefore essential but is based primarily on light microscopy, which is time consuming and can be limited by insufficient morphological characters such that more time is needed to examine critical features with electron microscopy. Monitoring with molecular tools is done in only a few places world-wide. EU FP7 MIDTAL (Microarray Detection of Toxic Algae) used SSU and LSU rRNA genes as targets on microarrays to identify toxic species. In order to comply with current monitoring requirements to report cell numbers as the relevant threshold measurement to trigger closure of fisheries, it was necessary to calibrate our microarray to convert the hybridisation signal obtained to cell numbers. Calibration curves for two species of Pseudo-nitzschia for use with the MIDTAL microarray are presented to obtain cell numbers following hybridisation. It complements work presented by Barra et al. (2012b. Environ. Sci. Pollut. Res. doi: 10.1007/s11356-012-1330-1v) for two other Pseudo-nitzschia spp., Dittami and Edvardsen (2012a. J. Phycol. 48, 1050) for Pseudochatonella, Blanco et al. (2013. Harmful Algae 24, 80) for Heterosigma, McCoy et al. (2013. FEMS. doi: 10.1111/1574-6941.12277) for Prymnesium spp., Karlodinium veneficum, and cf. Chatonella spp. and Taylor et al. (2014. Harmful Algae, in press) for Alexandrium.

Art, adolescence and Social Work: Anja, the invisible manager

This article has been written with the intention of being able to analyse the contributions of art —theatre, in this case— to the practice of social work. For this purpose, we have chosen to read the social reality in which we intervene through the lens of social constructionism. This helps us to rescue the social and subjective side of art, and, moreover, to recover the depathologization of the subject in professional intervention. Thus, using a practical case taken from work with adolescents in the German FSJ programme, hand-in-hand with a young girl called Anja we trace the developmental and sociological aspects of adolescence in order to later address certain common points of art and psychosocial work. Art will hence be redefined as a transitional object allowing questions to be addressed relating to (self-) perception, attachment, communication and changes in conduct as the ultimate goal of professional action. Lastly, we note the limitations and risks of art-based intervention, in order to conclude with a final synopsis.

Criminal Conversations: Rogues, Words and the World in the Work of Daniel Defoe

Even as Daniel Defoe's roguish protagonists notably Moll Flanders and Colonel Jack try to separate themselves from illicit itinerants, they are implicated further in deviance. Moll and Jack both embody and exploit ambiguous moral and spatial arrangements, and use hybrid linguistic formulations, all of which collocate the roguish and the reputable. By brilliantly realizing this interpenetration of words and worlds, Defoe problematises eighteenth-century efforts to demarcate the illicit and itinerant along the lines of space, rank, gender and language. Such efforts facilitated deviant mobility as much as they demonised it. Much scholarship has attended to Defoe's representations of criminality and poverty. This article develops such research to re-position him in a tradition of rogue-writing that stylishly problematises normative discriminatory practices.

Merely Birds of Passage: Lady Hariot Dufferin's Travel Writings and Medical Work in India, 1884-88

This article examines the travel writings and medical work in India of Lady Hariot Dufferin, Vicereine of India between 1884 and 1888. Lady Dufferin accompanied her husband, the Viceroy Lord Dufferin, through various social and political engagements in India, and carved her own niche in colonial and postcolonial history as a pioneer in the medical training of women in India. The article examines her travel writings on India and explores the nature of her complicity in the Raj, as well as the gendered nature of the separate public role she created for herself in relation to her 'zenana work' in providing medical care for the women of India. The author suggests that, through her work, Lady Dufferin challenges and extends the theoretical paradigms of postcolonialist and feminist critiques of empire.

Accessing Social Work Case Files for Research Purposes: Some Issues and Problems

The use of social work case files as an important research resource is being threatened by the increasing regulation of both the research process and access to personal identifiable information. While these developments can be seen as a reaction to specific incidents of inappropriate research and the misuse of personal information, it is argued that the pendulum has swung too far the other way, and in seeking to protect the rights of vulnerable individuals, the lives of these same individuals may go unstudied with the consequence that they receive less appropriate services. Drawing upon the current research of the authors, this article explores the difficulties encountered in gaining access to social work case files for research purposes without the explicit consent of service users and highlights the uncertainty surrounding this issue. Suggestions are made for improvements in the situation.