Regulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulum

The vast majority of secreted and membrane proteins are translated and folded at the endoplasmic reticulum (ER), where a sophisticated quality control mechanism ensures that only correctly folded proteins exit the ER and traffic to their final destinations. On the other hand, proteins that persistently misfold are eliminated through a process known as ER associated degradation (ERAD). This involves retrotranslocation of the misfolded protein through the ER membrane, and ubiquitination in advance of degradation by cytosolic proteasomes. The process of ERAD is best described in yeast where ubiquitin conjugating enzymes Ubc6p and Ubc7p function with a limited number of E3 ubiquitin ligases to ubiquitinate misfolded proteins. Interestingly, although the mechanistic principles of ERAD have been conserved through evolution, there is increasing evidence that homologues of the yeast enzymes have gained divergent roles and novel regulatory functions in higher eukaryotes, meaning that the process in humans is more complex and involves a larger repertoire of participating proteins. Two homologues of Ubc6p have been described in humans, and have been named as Ubc6 (UBE2J2) and Ubc6e (UBE2J1). However, little work has been done on these enzymes and thus our main objective of this study was to progress the functional characterisation of these ERAD E2 conjugating enzymes. Our studies included a detailed analysis of conditions whereby these proteins are stabilised and degraded. We’ve also explored the different molecular signalling pathways that induced changes on their steady state protein levels. Furthermore, Ubc6e has a phosphorylatable serine residue at position 184. Thus, our studies also involved delineating the signalling kinases that phosphorylate Ubc6e and examining its function in ERAD. Our studies confirm that the E2 Ubc enzymes are regulated posttranslationally and may have important implications in the regulation of ERAD.

Impact of protected forests on rural household fuel tree planting and deforestation: Chiro District, Ethiopia

This study aims at exploring the potential impact of forest protection intervention on rural households’ private fuel tree planting in Chiro district of eastern Ethiopia. The study results revealed a robust and significant positive impact of the intervention on farmers’ decisions to produce private household energy by growing fuel trees on their farm. As participation in private fuel tree planting is not random, the study confronts a methodological issue in investigating the causal effect of forest protection intervention on rural farm households’ private fuel tree planting through non-parametric propensity score matching (PSM) method. The protection intervention on average has increased fuel tree planting by 503 (580.6%) compared to open access areas and indirectly contributed to slowing down the loss of biodiversity in the area. Land cover/use is a dynamic phenomenon that changes with time and space due to anthropogenic pressure and development. Forest cover and land use changes in Chiro District, Ethiopia over a period of 40 years was studied using remotely sensed data. Multi temporal satellite data of Landsat was used to map and monitor forest cover and land use changes occurred during three point of time of 1972,1986 and 2012. A pixel base supervised image classification was used to map land use land cover classes for maps of both time set. The result of change detection analysis revealed that the area has shown a remarkable land cover/land use changes in general and forest cover change in particular. Specifically, the dense forest cover land declined from 235 ha in 1972 to 51 ha in 1986. However, government interventions in forest protection in 1989 have slowed down the drastic change of dense forest cover loss around the protected area through reclaiming 1,300 hectares of deforested land through reforestation program up to 2012.

Functional educational characterisation of the utility of embalming fluids for anatomical education and research

Human cadavers have long been used to teach human anatomy and are increasingly used in other disciplines. Different embalming techniques have been reported in the literature; however there is no clear consensus on the opinion of anatomists on the utility of embalmed cadavers for the teaching of anatomy. To this end, we aimed to survey British and Irish anatomy teachers to report their opinions on different preservation methods for the teaching of anatomy. In this project eight human cadavers were embalmed using formalin, Genelyn, Thiel and Imperial College London- Soft Preserving (ICL-SP) techniques to compare different characteristics of these four techniques. The results of this thesis show that anatomy teachers consider hard-fixed cadavers not to be the most accurate teaching model in comparison to the human body, although it still serves as a useful teaching method (Chapter 2). In addition, our findings confirm that joints of cadavers embalmed using ICL-SP solution faithfully mimics joints of an unembalmed cadaver compared to the other techniques (Chapter 3). Embalming a human body prevents the deterioration in the quality of images and our findings highlight that the influence of the embalming solutions varied with the radiological modality used (Chapter 4). The method developed as part of this thesis enables anatomists and forensic scientists to quantify the decomposition rate of an embalmed human cadaver (Chapter 5). Formalin embalming solution showed the strongest antimicrobial abilities followed by Thiel, Genelyn and finally by ICL-SP (Chapter 6). The overarching viewpoint of this set of studies show that it is inaccurate to state that one embalming technique is ultimately the best. The value of each technique differs based on the requirement of the particular education or research area. Hence we highlight how different embalming techniques may be better suited to certain fields of study.

In two minds about screening: an investigation of cervical cancer prevention among Irish women

Cervical cancer is the second most common female cancer worldwide. Cervical screening programmes can reduce the incidence of cervical cancer by up to 80 percent if the invited women participate. Previous Irish research has associated screening attendance with subjective norms, anticipated regret, higher socio-economic status and education. Greater perceived screening barriers and lacking knowledge were associated with avoidance. These findings support a variety of expectancy-value theories of behaviour. They also suggest that expectancy-value theories could benefit from the inclusion of affective predictors of behaviour, like anticipated regret. In 2008 the Republic of Ireland introduced the National Cervical Screening Programme (NCSP). This research seeks to identify the predictors of participation in the NCSP. A systematic review of reviews showed that predictors of screening participation clustered into environmental and psychological influences. There is a gap in the evidence synthesis of associations with personal characteristics and health beliefs. Thematic analysis of focus group interviews confirmed the validity of many screening predictors identified by the systematic review and expectancy-value theories. A survey of these predictors suggested that reduced screening barriers might encourage first-time participation, while regular attendance requires greater endorsement of screening benefits and stronger subjective norm and intention. Positive attitude, rather than knowledge, appeared to be crucial for strong intention, so the final study piloted an experiment comparing the utility of positive attitude in strengthening intention to the utility of information provision. Despite lacking significant differences between conditions, content analysis of participant comments suggested that a full trial would be worthwhile, given purposive sampling and improved sample retention. These findings agree with previous Irish research on the importance of screening intention, although its association with attitude appeared to be stronger in the present research. The findings further indicate that future screening promotion should consider interventions based on patients’ experiences of screening.

'Corkonian exceptionalism': identity, authenticity and the emotional politics of place in a small city's popular music scene

Drawing from ethnographic research on Cork city’s popular music scene, this article explores meanings of ‘authenticity’ as constructed through geographical, social and ideological referents. It unpacks local music producers’ position-takings within the local field of cultural production, and locates their narrative claims to authenticity with respect to the city’s strong sense of cultural identity. Their authenticating discourses are revealed as complex, often produced through building imagined communities of ‘us’ (in Cork) versus ‘them’ (in Dublin). The analysis indicates local actors’ deep sense of emotional attachment to place and to others within the music-making community, which impacts on their self-conception as creative labourers, sustains DIY, collaborative practices, and promotes a solidaristic ethos within the local music scene.

Postoperative analgesic effect, of preoperatively administered dexamethasone, after operative fixation of fractured neck of femur: randomised, double blinded controlled study.

Background: Fractured neck of femur is a common cause of hospital admission in the elderly and usually requires operative fixation. In a variety of clinical settings, preoperative glucocorticoid administration has improved analgesia and decreased opioid consumption. Our objective was to define the postoperative analgesic efficacy of single dose of dexamethasone administered preoperatively in patients undergoing operative fixation of fractured neck of femur. Methods: Institutional ethical approval was granted and written informed consent was obtained from each patient. Patients awaiting for surgery at Cork University Hospital were recruited between July 2009 and August 2012. Participating patients, scheduled for surgery were randomly allocated to one of two groups (Dexamethasone or Placebo). Patients in the dexamethasone group received a single dose of intravenous dexamethasone 0.1 mg kg -1 immediately preoperatively. Patients in the placebo group received the same volume of normal saline. Patients underwent operative fixation of fractured neck of femur using standardised spinal anaesthesia and surgical techniques. The primary outcome was pain scores at rest 6 h after the surgery. Results: Thirty seven patients were recruited and data from thirty patients were analysed. The groups were similar in terms of patient characteristics. Pain scores at rest 6 h after the surgery (the principal outcome) were lesser in the dexamethasone group compared with the placebo group [0.8(1.3) vs. 3.9(2.9), mean(SD) p = 0.0004]. Cumulative morphine consumption 24 h after the surgery was also lesser in the dexamethasone group [7.7(8.3) vs. 15.1(9.4), mean(SD) mg, p = 0.04]. Conclusions: A single dose of intravenous dexamethasone 0.1 mg kg -1 administered before operative fixation of fractured neck of femur improve significantly the early postoperative analgesia. Trial registration: ClinicalTrials.gov identifier: NCT01550146, date of registration: 07/03/2012

Magnetic susceptibility and ice-rafted debris in surface sediments of the Nordic Sea

Magnetic susceptibility and ice-rafted debris of surface sediments in the Nordic Seas were investigated to reconstruct source areas and recent transport pathways of magnetic minerals. From the distribution of magnetic susceptibility and ice-rafted debris and published data on petrographic tracers for iceberg drift, we reconstructed a counter-clockwise iceberg drift pattern during cooler phases in the Holocene, which is similar to conceptual and numerical models for Weichselian iceberg drift. The release of basaltic debris at Scoresby Sund played a significant role for the magnetic signature of stadial/interstadial events during isotope stage 3 recorded in sediment cores of the Nordic Seas.

The gendered effects of family migration law: contextual interpretation as a possible judicial remedy

At all normative levels, family migration law can disproportionally and negatively affect immigrant women’s rights in this field, producing gendered effects. In some cases, such effects are related to the normative and judicial imposition of unviable family-related models (e.g., the ʻgood mother ̕ the one-breadwinner family, or a rigid distinction between productive and reproductive work). In other cases, they are due to family migration law’s overlooking of the specific needs and difficulties of immigrant women, within their families and in the broader context of their host countries’ social and normative framework.To effectively expose and correct this gender bias, in this article I propose an alternative view of immigrant women’s right to family life, as a cluster of rights and entitlements rather than as a mono-dimensional right. As a theoretical approach, this construction is better equipped to capture the complex experiences of immigrant women in the European legal space, and to shed light on the gendered effects generated not by individual norms but by the interaction of norms that are traditionally assigned to separated legal domains (e.g., immigration law and criminal law). As a judicial strategy, this understanding is capable of prompting a consideration by domestic and supranational courts of immigrant women not as isolated individuals, but as ‘individuals in context’. I shall define this type of approach as ‘contextual interpretation’, understood as the consideration of immigrant women in the broader contexts of their families, their host societies and the normative frameworks applicable to them. Performed in a gendersensitive manner, a contextual judicial interpretation has the potential to neutralize the gendered effects of certain family migration norms. To illustrate these points, I will discuss selected judicial examples offered by the European Court on Human Rights, as well as from domestic jurisdictions of countries with a particularly high incidence of immigrant women (Italy and Spain).

The iceberg of suicide and self-harm in Irish adolescents: a population-based study

PURPOSE Suicide is a leading cause of death among adolescents. Self-harm is the most important risk factor for suicide, yet the majority of self-harm does not come to the attention of health services. The purpose of this study was to establish the relative incidence of adolescent suicide, hospital-treated self-harm and self-harm in the community. METHODS Annual suicide rates were calculated for 15-17 year-old in the Cork and Kerry region in Ireland based on data from the Central Statistics Office. Rates of hospital-treated self-harm were collected by the Irish National Registry of Deliberate Self-Harm. Rates of self-harm in the community were assessed using a survey of 3,881 adolescents, the Child and Adolescent Self-harm in Europe study. RESULTS The annual suicide rate was 10/100,000. Suicide was six times more common among boys than girls. The annual incidence rate of hospital-treated self-harm was approximately 344/100,000, with the female rate almost twice the male rate. The rate of self-harm in the community was 5,551/100,000, and girls were almost four times more likely to report self-harm. For every boy who died by suicide, 16 presented to hospital with self-harm and 146 reported self-harm in the community. For every female suicide, 162 girls presented to hospital with self-harm and 3,296 reported self-harm. CONCLUSIONS Gender differences in relative rates of self-harm and suicide are very large, with boys who have harmed themselves at particularly high risk of suicide. Knowledge of the relative incidence of self-harm and suicide in adolescents can inform prevention programmes and services.

Treatment of phenanthrene and benzene using microbial fuel cells operated continuously for possible in situ and ex situ applications

Bioelectrochemical systems could have potential for bioremediation of contaminants either in situ or ex situ. The treatment of a mixture of phenanthrene and benzene using two different tubular microbial fuel cells (MFCs) designed for either in situ and ex situ applications in aqueous systems was investigated over long operational periods (up to 155 days). For in situ deployments, simultaneous removal of the petroleum hydrocarbons (>90% in term of degradation efficiency) and bromate, used as catholyte, (up to 79%) with concomitant biogenic electricity generation (peak power density up to 6.75 mWm−2) were obtained at a hydraulic retention time (HRT) of 10 days. The tubular MFC could be operated successfully at copiotrophic (100 ppm phenanthrene, 2000 ppm benzene at HRT 30 days) and oligotrophic (phenanthrene and benzene, 50 ppb each, HRT 10 days) substrate conditions suggesting its effectiveness and robustness at extreme substrate concentrations in anoxic environments. In the MFC designed for ex situ deployments, optimum MFC performance was obtained at HRT of 30 h giving COD removal and maximum power output of approximately 77% and 6.75 mWm−2 respectively. The MFC exhibited the ability to resist organic shock loadings and could maintain stable MFC performance. Results of this study suggest the potential use of MFC technology for possible in situ/ex situ hydrocarbon-contaminated groundwater treatment or refinery effluents clean-up, even at extreme contaminant level conditions.