Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)

The pursuit of happiness: the social and scientific origins of Hans Selye’s natural philosophy of life

© The Author(s) 2012. Open access article.In 1956, Hans Selye tentatively suggested that the scientific study of stress could ‘help us to formulate a precise program of conduct’ and ‘teach us the wisdom to live a rich and meaningful life’. Nearly two decades later, Selye expanded this limited vision of social order into a full-blown philosophy of life. In Stress without Distress, first published in 1974, he proposed an ethical code of conduct designed to mitigate personal and social problems. Basing his arguments on contemporary understandings of the biological processes involved in stress reactions, Selye referred to this code as ‘altruistic egotism’. This article explores the origins and evolution of Selye’s ‘natural philosophy of life’, analysing the links between his theories and adjacent intellectual developments in biology, psychosomatic and psychosocial medicine, cybernetics and socio-biology, and situating his work in the broader cultural framework of modern western societies.Wellcome Trus

Awards, Archives, and Affects: Tropes in the World Press Photo Contest 2009 - 2011

__Abstract__ Photography contests have assumed an increasingly significant public role in the context of the global surge of mass-mediated war reporting. This study focuses on the recurrence of visual tropes in press photographs awarded in the annual contest World Press Photo (WPP) in the years 2009–11. By tropes, we mean conventions (e.g. a mourning woman, a civilian facing soldiers, a distressed witness to an atrocity) that remain unchanged despite their travels across the visual sphere, gaining professional and public recognition and having a strong affective impact. We contend that photography contests such as the WPP influence and organize a process of generic understanding of war, disaster and atrocity that is based on a number of persistent tropes, such as the mourner, the protester or the survivor amidst chaos and ruins. We further show that these tropes are gendered along traditional conceptions of femininity and masculinity, appealing strongly to both judges and wider audiences. The evidence for our claim comes from an analysis of the photographs that won awards, observation of the judging sessions, semi-structured interviews with three jury chairmen, and public commentary on the juries’ choices (blogs, newspapers and websites)

Hidden, visceral and traumatic: a dramaturgical approach to men talking about their penis after surgery for penile cancer

YesDrawing upon concepts of expressive equipment and body image, the aim of this study is to explore how men diagnosed and treated for penile cancer construct their penis and its surgical disfigurement (penectomy). Using maximum variation sampling with the intention to acquire the broadest range of experiences of stage of disease and treatment, 27 cisgender men (aged 48-83, x=63) who had surgical treatment consented for their data to be archived for analysis. From a dramaturgical perspective, the constructionist thematic analysis explored direct and indirect talk about the penis after surgery. The analysis showed that through graphic and sequential narratives of dismemberment revealed, participants constructed a post-surgery period in which they both wanted and did-not-want to see their penis. Additionally, participants constructed themselves managing difficult emotions through others and seeing themselves being rejected by a potentially desiring (female) Other. The findings extend research on male genitals by showing how the post-surgery penis can function as something hidden but visceral and traumatic when revealed. Importantly, this paper illustrates body image as expressive equipment where body and identity are formed in the image of manhood, which is an intersubjective (sexual) object between self and other.This paper presents independent research commissioned by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0808-17158).Research Development Fund Publication Prize Award winner, October 2019

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

Abstract Background Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Results Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Conclusion Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. Trial Registration ClinicalTrials.gov NCT0029074