Targeting the EP1 receptor reduces Fas ligand expression and increases the antitumor immune response in an in vivo model of colon cancer

Despite studies demonstrating that inhibition of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has significant chemotherapeutic benefits in vitro and in vivo, inhibition of COX enzymes is associated with serious gastrointestinal and cardiovascular side effects, limiting the clinical utility of these drugs. PGE2 signals through four different receptors (EP1–EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. Here, we show that targeted inhibition of the EP1 receptor in the tumor cells and the tumor microenvironment resulted in the significant inhibition of tumor growth in vivo. Both dietary administration and direct injection of the EP1 receptor-specific antagonist, ONO-8713, effectively reduced the growth of established CT26 tumors in BALB/c mice, with suppression of the EP1 receptor in the tumor cells alone less effective in reducing tumor growth. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4+CD25+Foxp3+ regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased. F4/80+ macrophage infiltration was also decreased; however, there was no change in macrophage phenotype. These findings suggest that the EP1 receptor represents a potential target for the treatment of colon cancer.

Work experience in transition year: a mixed methods study of subject and career choices

Transition Year (TY) has been a feature of the Irish Education landscape for 39 years. Work experience (WE) has become a key component of TY. WE is defined as a module of between five and fifteen days duration where students engage in a work placement in the broader community. It places a major emphasis on building relationships between schools and their external communities and concomitantly between students and their potential future employers. Yet, the idea that participation in a TY work experience programme could facilitate an increased awareness of potential careers has drawn little attention from the research community. This research examines the influence WE has on the subsequent subjects choices made by students along with the effects of that experience on the students’ identities and emerging vocational identities. Socio-cultural Learning Theory and Occupational Choice Theory frame the overall study. A mixed methods approach to data collection was adopted through the administration of 323 quantitative questionnaires and 32 individual semi-structured interviews in three secondary schools. The analysis of the data was conducted using a grounded theory approach. The findings from the research show that WE makes a significant contribution to the students’ sense of agency in their own lives. It facilitates the otherwise complex process of subject choice, motivates students to work harder in their senior cycle, introduces them to the concepts of active, experience-based and self-directed learning, while boosting their self-confidence and nurturing the emergence of their personal and vocational identities. This research is a gateway to further study in this field. It also has wide reaching implications for students, teachers, school authorities, parents and policy makers regarding teaching and learning in our schools and the value of learning beyond the walls of the classroom.

Expression and function of the neurotrophic factors GDF5 and GDNF in the nigrostriatal system during development and in rat models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD), and may represent promising new therapies for PD. The aim of the present study was to investigate the endogenous expression and function of GDF5 and GDNF in the nigrostriatal dopaminergic system during development and in rat models of PD. Examination of the temporal expression patterns of endogenous GDF5, GDNF, and their respective receptors, in the developing and adult nigrostriatal dopaminergic system suggest that these factors play important roles in promoting the survival and maturation of midbrain dopaminergic neurons during the period of postnatal programmed cell death. The relative levels of GDF5 and GDNF mRNAs in the midbrain and striatum, and their individual temporal expression patterns during development, suggest that their modes of actions are quite distinct in vivo. Furthermore, the sustained expression of GDF5, GDNF, and their receptors into adulthood suggest roles for these factors in the continued support and maintenance of mature nigrostriatal dopaminergic neurons. The present study found that endogenous GDF5, GDNF, and their receptors are differentially expressed in two 6-hydroxydopamine-induced lesion adult rat models of PD. In both terminal and axonal lesion models of PD, GDF5 mRNA levels in the striatum increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased at 10 and 28 days post-lesion. Thus, despite the fact that exogenous GDF5 and GDNF have similar effects on midbrain dopaminergic neurons in vitro and in vivo, their endogenous responses to a neurotoxic injury are quite distinct. These results highlight the importance of studying the temporal dynamic changes in neurotrophic factor expression during development and in animal models of PD.

Properties and applications of injection locking in 1.55 μm quantum-dash mode-locked semiconductor lasers

Mode-locked semiconductor lasers are compact pulsed sources with ultra-narrow pulse widths and high repetition-rates. In order to use these sources in real applications, their performance needs to be optimised in several aspects, usually by external control. We experimentally investigate the behaviour of recently-developed quantum-dash mode-locked lasers (QDMLLs) emitting at 1.55 μm under external optical injection. Single-section and two-section lasers with different repetition frequencies and active-region structures are studied. Particularly, we are interested in a regime which the laser remains mode-locked and the individual modes are simultaneously phase-locked to the external laser. Injection-locked self-mode-locked lasers demonstrate tunable microwave generation at first or second harmonic of the free-running repetition frequency with sub-MHz RF linewidth. For two-section mode-locked lasers, using dual-mode optical injection (injection of two coherent CW lines), narrowing the RF linewidth close to that of the electrical source, narrowing the optical linewidths and reduction in the time-bandwidth product is achieved. Under optimised bias conditions of the slave laser, a repetition frequency tuning ratio >2% is achieved, a record for a monolithic semiconductor mode-locked laser. In addition, we demonstrate a novel all-optical stabilisation technique for mode-locked semiconductor lasers by combination of CW optical injection and optical feedback to simultaneously improve the time-bandwidth product and timing-jitter of the laser. This scheme does not need an RF source and no optical to electrical conversion is required and thus is ideal for photonic integration. Finally, an application of injection-locked mode-locked lasers is introduced in a multichannel phase-sensitive amplifier (PSA). We show that with dual-mode injection-locking, simultaneous phase-synchronisation of two channels to local pump sources is realised through one injection-locking stage. An experimental proof of concept is demonstrated for two 10 Gbps phase-encoded (DPSK) channels showing more than 7 dB phase-sensitive gain and less than 1 dB penalty of the receiver sensitivity.

Evaluation of microbial adjuncts and their effect on the ripening of cheddar cheese

A bacteriocin-producing strain of Lactobacillus paracasei DPC 4715 was used as an adjunct culture in Cheddar cheese in order to control the growth of “wild” nonstarter lactic acid bacteria. No suppression of growth of the indicator strain was observed in the experimental cheese. The bacteriocin produced by Lactobacillus paracasei DPC 4715 was sensitive to chymosin and cathepsin D and it may have been cleaved by the rennet used for the cheese manufactured or by indigenous milk proteases. A series of studies were performed using various microbial adjuncts to influence cheese ripening. Microbacterium casei DPC 5281, Corynebacterium casei DPC 5293 and Corynebacterium variabile DPC 5305 were added to the cheesemilk at level of 109 cfu/ml resulting in a final concentration of 108 cfu/g in Cheddar cheese. The strains significantly increased the level of pH 4.6-soluble nitrogen, total free amino acids after 60 and 180 d of ripening and some individual free amino acids after 180 d. Yarrowia lipolytica DPC 6266, Yarrowia lipolytica DPC 6268 and Candida intermedia DPC 6271 were used to accelerate the ripening of Cheddar cheese. Strains were grown in YG broth to a final concentration of 107 cfu/ml, microfluidized, freeze-dried and added to the curd during salting at level of 2% w/w. The yeasts positively affected the primary, secondary proteolysis and lipolysis of cheeses and had aminopeptidase, dipeptidase, esterase and 5’ phosphodiestere activities that contributed to accelerate the ripening and improve the flavor of cheese. Hafia alvei was added to Cheddar cheesemilk at levels of 107 cfu/ml and 108 cfu/ml and its contribution during ripening was evaluated. The strain significantly increased the level of pH 4.6-soluble nitrogen, total free amino-acids, and some individual free amino-acids of Cheddar cheese, whereas no differences in the urea-polyacrylamide gel electrophoresis (urea-PAGE) electrophoretograms of the cheeses were detected. Hafia alvei also significantly increased the level of some biogenic amines. A low-fat Cheddar cheese was made with Bifidobacterium animalis subsp. lactis, strain BB-12® at level of 108 cfu/ml, as a probiotic adjunct culture and Hi-Maize® 260 (resistant high amylose maize starch) at level of 2% and 4% w/v, as a prebiotic fiber which also played the role of fat replacer. Bifidobacterium BB-12 decreased by 1 log cycle after 60 d of ripening and remained steady at level of ~107 cfu/g during ripening. The Young’s modulus also increased proportionally with increasing levels of Hi-maize. Hencky strain at fracture decreased over ripening and increased with increasing in fat replacer. A cheese based medium (CBM) was developed with the purpose of mimicking the cheese environment at an early ripening stage. The strains grown in CBM showed aminopeptidase activity against Gly-, Arg-, Pro- and Phe-p-nitroanalide, whereas, when grown in MRS they were active against all the substrates tested. Both Lb. danicus strains grown in MRS and in CBM had aminotransferase activity towards aromatic amino acids (Phe and Trp) and also branched-chain amino acids (Leu and Val). Esterase activity was expressed against p-nitrophenyl-acetate (C2), pnitrophenyl- butyrate (C4) and p-nitrophenyl-palmitate (C16) and was significantly higher in CBM than in MRS.

Continuity and change in monetary policy and banking in Ireland 1922-43

The primary objective of this thesis is to examine the development of monetary policy and banking in southern Ireland from the attainment of independence in 1922 (gained through the Anglo-Irish Treaty of 1921) to the establishment of the Central Bank of Ireland in 1943. This research serves to challenge the overwhelming concentration on the findings of a small number of major works, most notably by Ronan Fanning, Maurice Moynihan and Cormac Ó’Gráda, in the existing historiography. This thesis is based on the research hypothesis that there were two key factors impacting on the development of monetary and banking institutions in Ireland in the 1922-1943 period. First, an exogenous institutional context, primarily Anglo-Irish in focus, in which the wider macroeconomic landscape directly influenced monetary policy and banking in Ireland. Second, an individualist context in which the development of relationships between key individuals dictated development patterns and institutional structures. This research highlights that key Irish policymakers, such as Joseph Brennan, evidenced a more flexible and realistic approach to banking and monetary affairs than is currently recognised. It also develops three further issues which have been overlooked in the existing historiography. First, a germ of monetary reform existed in Ireland from as early as the mid-1920s and was consistent in promoting alternative policies in the period to 1943. Second, this research challenges the view that the creation of the Currency Commission in 1927 and the establishment of the Central Bank of Ireland in 1943 were insignificant events given the continued stagnation in Irish monetary policy in the decades after 1943. Third, this thesis identifies that wider international trends did influence Irish monetary and banking affairs in the 1922-43 period. At both an institutional and more individual level the process of monetary institution building in Ireland was directly impacted by wider international experiences.

Childhood obesity in Ireland: recent trends and modifiable determinants

Background: Childhood obesity is a global epidemic posing a significant threat to the health and wellbeing of children. To reverse this epidemic, it is essential that we gain a deeper understanding of the complex array of driving factors at an individual, family and wider ecological level. Using a social-ecological framework, this thesis investigates the direction, magnitude and contribution of risk factors for childhood overweight and obesity at multiple levels of influence, with a particular focus on diet and physical activity. Methods: A systematic review was conducted to describe recent trends (from 2002-2012) in childhood overweight and obesity prevalence in Irish school children from the Republic of Ireland. Two datasets (Cork Children’s Lifestyle [CCLaS] Study and the Growing Up in Ireland [GUI] Study) were used to explore determinants of childhood overweight and obesity. Individual lifestyle factors examined were diet, physical activity and sedentary behaviour. The determinants of physical activity were also explored. Family factors examined were parental weight status and household socio-economic status. The impact of food access in the local area on diet quality and body mass index (BMI) was investigated as an environmental level risk factor. Results: Between 2002 and 2012, the prevalence of childhood overweight and obesity in Ireland remained stable. There was some evidence to suggest that childhood obesity rates may have decreased slightly though one in four Irish children remained either overweight or obese. In the CCLaS study, overweight and obese children consumed more unhealthy foods than normal weight children. A diet quality score was constructed based on a previously validated adult diet score. Each one unit increase in diet quality was significantly associated with a decreased risk of childhood overweight and obesity. Individual level factors (including gender, being a member of a sports team, weight status) were more strongly associated with physical activity levels than family or environmental factors. Overweight and obese children were more sedentary and less active than normal weight children. There was a dose response relationship between time spent at moderate to vigorous physical activity (MVPA) and the risk of childhood obesity independent of sedentary time. In contrast, total sedentary time was not associated with the risk of childhood obesity independent of MVPA though screen time was associated with childhood overweight and obesity. In the GUI Study, only one in five children had 2 normal weight parents (or one normal weight parent in the case of single parent families). Having overweight and obese parents was a significant risk factor for overweight and obesity regardless of socio-economic characteristics of the household. Family income was not associated with the odds of childhood obesity but social class and parental education were important risk factors for childhood obesity. Access to food stores in the local environment did not impact dietary quality or the BMI of Irish children. However, there was some evidence to suggest that the economic resources of the family influenced diet and BMI. Discussion: Though childhood overweight and obesity rates appear to have stabilised over the previous decade, prevalence rates are unacceptably high. As expected, overweight and obesity were associated with a high energy intake and poor dietary quality. The findings also highlight strong associations between physical inactivity and the risk of overweight and obesity, with effect sizes greater than what have been typically found in adults. Important family level determinants of childhood overweight and obesity were also identified. The findings highlight the need for a multifaceted approach, targeting a range of modifiable determinants to tackle the problem. In particular, policies and interventions at the shared family environment or community level may be an effective mean of tackling this current epidemic.

A river of memory: landscape, narrative and identity in the Lee Valley, Co. Cork, Ireland

In moments of rapid social changes, as has been witnessed in Ireland in the last decade, the conditions through which people engage with their localities though memory, individually and collectively, remains an important cultural issue with key implications for questions of heritage, preservation and civic identity. In recent decades, cultural geographers have argued that landscape is more than just a view or a static text of something symbolic. The emphasis seems to be on landscape as a dynamic cultural process – an ever-evolving process being constructed and re-constructed. Hence, landscape seems to be a highly complex term that carries many different meanings. Material, form, relationships or actions have different meanings in different settings. Drawing upon recent and continuing scholarly debates in cultural landscapes and collective memory, this thesis sets out to examine the generation of collective memory and how it is employed as a cultural tool in the production of memory in the landscape. More specifically, the research considers the relationships between landscape and memory, investigating the ways in which places are produced, appropriated, experienced, sensed, acknowledged, imagined, yearned for, appropriated, re-appropriated, contested and identified with. A polyvocal-bricoleur approach aims to get below the surface of a cultural landscape, inject historical research and temporal depth into cultural landscape studies and instil a genuine sense of inclusivity of a wide variety of voices (role of monuments and rituals and voices of people) from the past and present. The polyvocal-bricoleur approach inspires a mixed method methodology approach to fieldsites through archival research, fieldwork and filmed interviews. Using a mixture of mini-vignettes of place narratives in the River Lee valley in the south of Ireland, the thesis explores a number of questions on the fluid nature of narrative in representing the story and role of the landscape in memory-making. The case studies in the Lee Valley are harnessed to investigate the role of the above questions/ themes/ debates in the act of memory making at sites ranging from an Irish War of Independence memorial to the River Lee’s hydroelectric scheme to the valley’s key religious pilgrimage site. The thesis investigates the idea that that the process of landscape extends not only across space but also across time – that the concept of historical continuity and the individual and collective human engagement and experience of this continuity are central to the processes of remembering on the landscape. In addition the thesis debates the idea that the production of landscape is conditioned by several social frames of memory – that individuals remember according to several social frames that give emphasis to different aspects of the reality of human experience. The thesis also reflects on how the process of landscape is represented by those who re-produce its narratives in various media.

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

PURPOSE: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. PATIENTS AND METHODS: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. RESULTS: Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative. CONCLUSION: No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Diversity and Inclusion at UMD Libraries Survey Results

The survey was made available online to library faculty, staff, and student workers. Participation in the survey was completely voluntary, and each individual question was entirely optional. In accordance with UMD policy, responses were treated as confidential. Fewer than five responses in a particular category were considered identifiable by the U.S. Department of Education and were not included in this report. Those who participated in the survey represent a significant portion of the Libraries’ community.

Workplace violence and intentions to quit: results from a survey of London nurses

Study Objective: Work-place violence, harassment and abuse is an increasing feature of nurses’ experience of work in many countries. There is some evidence that the experience of workplace violence affects levels of job satisfaction (Hesketh et al 2003) and career decisions (e.g. Mayer et al 1999, Fernandes et al 1999). This paper reports on verbal and physical abuse by patients, relatives and carers, as well as racial and sexual harassment in Acute Hospitals in London and investigates whether workplace violence affects nurses’ intentions to leave either their current job or the nursing profession, controlling for a number of other factors that are known to affect career decisions, such as workload, pay and own health. Method: A questionnaire designed by two of the authors (Reeves and West) to assess many different aspects of nurses work life was used in a postal survey of nurses grades A to I practising in twenty London acute trusts in 2002. A total of 6,160 clinical nurses were mailed the questionnaires and 2,880 returned completed questionnaires, resulting in an overall response rate of 47%, discounting undelivered questionnaires. Respondents worked in a wide variety of clinical settings but mainly in acute medical and surgical wards. In addition to descriptive statistics, results were analysed using logistic regression with robust standard errors: the appropriate test when the dependent variable is dichotomous and the individual respondents clustered within units (nurses working within hospitals are not statistically independent). Results: Our results show high levels of racial (%), sexual (%) and other, unspecified forms of harassment (%), as well as verbal and physical abuse (14% had been physically assaulted with 5% being assaulted more than once), over the previous 6 months. A very small number (1%) reported experiencing all three forms of harassment; 12% two forms and 29% one form. Only 45% of this sample intended to stay in nursing for at least 3 years; 40% were undecided and 15% intended to leave. Logistic regression estimates showed that reported levels of abuse and harassment had a significant impact on respondents’ career intentions, even in models that controlled for known factors affecting career decisions. About 70% of our respondents reported that they had had too little training in dealing with aggressive behaviour—or none at all—but there was no statistical relationship between lack of training and reported assaults. Conclusions: The international shortage of health care workers is due at least in part to low retention rates. It is crucial to investigate nurses’ experiences of work to identify the factors that shape their career decisions. Workplace violence is increasingly acknowledged as an international, service-wide, health care problem. This paper adds to the literature that shows that workplace violence has an impact on nurses’ career decisions. The implications for managers and policy makers are that strengthening systems of security and providing nurses with training in interpersonal relationships including dealing with aggressive patients could slow nurse turnover.

Playback Theatre: the art of being oneself. A tool for empowerment and real change for individuals and communities

This article presents the application of a theatrical technique—Playback Theatre, which was developed in the United States during the 1970s—to social intervention, as a narrative and listening space that confers value and dignity upon the person and the unique and distinct individual experiences that facilitate their social and relational integration. This art of being oneself, as the author states, uses the oral tradition and spontaneous and creative communication of psychodrama and combines them with theatrical expression. This technique has been shown to be pertinent to both community social work and support groups for persons in problematic situations. The aim of this is to celebrate some specific moment of their lives, as individuals or as a community, and to define strategies for improving living conditions or resolving or alleviating conflicts. It is also used to assess the achievements of the proposed objectives, to strengthen the motivation to change and to transform existing relationships into collaborative ones. This is possible not only owing to the participation of persons, but also to the assumption of different roles that can permit the overcoming of certain traumatic events.In addition to support groups, it is used for the training and supervision of social work professionals. The theatrical technique in question allows them to assume roles as diverse as narrator, audience or actor, whether simultaneously or successively. Taking the role of «performer» or guide to the theatrical action requires prior preparation in order for the group of participants to be able to pool their individualities and their emotions and reflect on them. The participatory methodology that Playback Theatre proposes is important in community social work and is posed in a new and transformative key.

Monoamines and decision making during contests in the hermit crab Pagurus bernhardus

During fights animals are expected to make a series of strategic decisions that involve interactions between information about the contest and the individual's nervous system that produce a change in behaviour. Biogenic monoamines such as serotonin ('5-HT') and dopamine are thought to prime decision-making centres for appropriate responses during aggressive interactions in crustaceans, and circulating levels vary both between individuals and during agonistic encounters. Aminergenic systems operate in diverse animal taxa and in this study we assayed circulating levels of S-HT and dopamine following shell fights in the common European hermit crab, Pagurus bernhardus. The two roles in these fights, attacker and defender, perform different activities but, in both, S-HT increased and dopamine declined in response to engaging in a fight. In defenders but not attackers, giving up was correlated with low 5-HT and dopamine. In attackers, motivation to initiate a fight was positively correlated with dopamine levels. Circulating monoamines are therefore involved in decision making during these aggressive encounters. (c) 2007 The Association for the Study of Animal Behaviour Published by Elsevier Ltd. All rights reserved.

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Cytosol protein regulation in H295R steroidogenesis model induced by the zearalenone metabolites, α- and β-zearalenol.

a- and b-zearalenol (a-ZOL and b-ZOL, respectively) are metabolites of the mycotoxin zearalenone (ZEN). All three individual mycotoxins have shown to be biological active i.e. being estrogenic and able to stimulate cellular proliferation albeit at different strengths. In this work, cytosol protein expression was determined by using stable-isotope labelling by amino acids in cell culture (SILAC) upon exposure of a-ZOL and b-ZOL to the steroidogenesis cell model H295R. A total of 14 and 5 individual proteins were found to be significantly regulated by a-ZOL and b-ZOL, respectively. Interestingly, there were no common protein regulations by the metabolites or the parent mycotoxin ZEN. Furthermore, the regulated proteins were assigned to networks and groups of actions that also differed from one another suggesting that the three individual mycotoxins may have unique biological activities.