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.

Saothair Oideachais an Ghúim 1926-46

Ceann de phrionsabail bhunaidh An Ghúim téacsleabhair agus leabhair ghinearálta a sholáthar do dhaltaí scoile is do lucht léitheoireachta na Gaeilge. Ábhair a bhaineann le curaclam na scoile, cuir i gcás, eolaíocht is tíos, oideachas, saoránaíocht, spórt, na teangacha Clasaiceacha, tíreolaíocht, taisteal agus an nádúr, creideamh is stair, a roghnaítear don taighde seo. Tugtar Aguisín (921 lch) le bheith ina threoir do phríomh-bhunachar sonraí na dochtúireachta seo (an chiall ghinearálta mar bhailiúchán eolais atá i gceist le “bunachar” sa tráchtas seo in ionad brí theicniúil ar leith). Trí phríomhchuid atá sa staidéar: “buneolas”, “anailís” is “toradh”. Sa “Bhuneolas”, tugtar cuntas beathaisnéiseach ar na bunúdair, soláthraítear achoimre ar na foilseacháin faoi staidéar, mar aon le faisnéis bhibleagrafaíochta i dtaobh na n- aistritheoirí, agus eolas faoi na comhlachtaí foilsitheoireachta a bhí páirteach sna tograí. Pléann “Anailís” brainsí de chuid an státchórais mar an Roinn Oideachais agus an Roinn Airgeadais i gcúrsaí maoinithe, nó gníomhairí lasmuigh de, cosúil le lucht deartha is clóchuradóireachta; moladh is coimisiúnú na saothar; sonraí cóipchirt na bhfoilseachán; roghnú, monatóireacht is díolaíocht na n-aistritheoirí, mar aon le breithniú inmheánach is seachtrach. Sa chuid dheireanach, féachtar le “Toradh” na hiarrachta a mheas, ag tagairt den líon cóipeanna de na leabhair a díoladh. Faightear eolas ar fhiosrú léitheoirí; praghas na leabhar; a ndíolachán is a n- athchló. Tugtar léirmheasanna a scríobhadh ar na haistriúcháin Ghaeilge agus na cúiseanna nár tháinig tograí ar leith chun críche. Is é aidhm na hoibre thar aon ní eile gné lárnach chasta d’eisint An Ghúim atá ligthe i ndíchuimhne a thabhairt ar ais chugainn go beo beathaíoch faoi mar a bhí lena ré saoil féin.

Interspecific competition between the potato cyst nematode species Globodera pallida and G. rostochiensis

The two potato cyst nematode species, Globodera pallida and G. rostochiensis, are among the most important pests of potato. PCN are difficult to manage, while the two species respond differently to the main control methods. An increase in the incidence of G. pallida had been reported and is generally attributed to greater effectiveness of control measures against G. rostochiensis. The status of PCN in Ireland was studied using PCR. The results demonstrated qPCR to be an efficient means of high-throughput PCN sampling, being able to accurately identify both species in mixed-species populations. Species discrimination using qPCR revealed an increase in the incidence of G. pallida in Ireland in the absence of G. pallida-selective control measures. The population dynamics of G. pallida and G. rostochiensis in Ireland were studied in mixed- and single-species competition assays in vivo. G. pallida proved to be the more successful species, with greater multiplication in mixed- than single-species populations, with G. rostochiensis showing the opposite. This effect was similarly observed in staggered inoculation trials and population proportion trials. It was hypothesised that the greater G. pallida competitiveness could be attributed to its later hatch. G. pallida exhibited a later peak in hatching activity and more prolonged hatch, relative to G. rostochiensis. G. rostochiensis hatch was significantly reduced in mixedspecies hatching assays. G. pallida hatch was significantly higher when hatch was induced in potato root leachates containing G. rostochiensis-specific compounds, indicating that G. pallida hatch is stimulated upon perception of G. rostochiensis–derived compounds. Rhizotron studies revealed that root damage, caused by feeding of the early-hatching G. rostochiensis, resulted in increased lateral root proliferation and significantly increased G. pallida multiplication. Split-root trials indicated a significant G. pallida-induced ISR effect. G. rostochiensis multiplication was significantly reduced in split-root rhizotrons when G. pallida colonised roots before or after G. rostochiensis infection.

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.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Aim: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). Method: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. Results: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. Interpretation: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

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).

La música en el desarrollo de la espiritualidad y la religiosidad. Una aproximación al Cristianismo y al Budismo

La música puede afectar al individuo en todos sus niveles –físico, mental y espiritual–. El presente artículo se centra en el papel que ésta desempeña en el desarrollo de la vida espiritual y trascendental. Para ello, realizaremos un repaso histórico de su evolución estética y social, abordaremos dicho fenómeno a nivel fisiológico y presentaremos sus aplicaciones clínicas y sociales. Seguidamente y a modo de ejemplo de las concepciones de pensamiento occidental y oriental, trataremos la forma en que el cristianismo y el budismo conciben la música dentro de su doctrina. Finalizaremos con algunas reflexiones sobre el tema.