Starvation-induced alterations in hepatic lysine metabolism in different families of rainbow trout (Oncorhynchus mykiss)

This study focused on lysine catabolism by the lysine alpha-ketoglutarate reductase (LKR) pathway in rainbow trout (RBT). Selective breeding based on feed efficiency in 2 strains (A and B) of RBT generated 2 families within each strain. Eight fish from each of the four families were randomly allotted to individual tanks. Fish were fed until satiation for 3 wks at which time four fish within each family were randomly selected for 2 wks of starvation. After the 2 wk starvation, all fish were harvested. Hepatic in-vitro LKR activity and lysine oxidation (LOX) were measured as was LKR mRNA abundance. Strain A exhibited a 55% reduction in LKR transcripts compared to strain B pooled across both feeding levels (P \u3c 0.01). LKR mRNA was decreased (P \u3c 0.01) in starved versus fed fish. No differences were detected for LKR activity and LOX between fed and starved fish, between strains or between families. LKR transcripts were positively correlated to weight gain (p \u3c 0.01)

Parturition, oxytocin, inflammation, myocyte damage and obesity; A study of myometrium and haematological parameters in human pregnancy and labour at term

The process of parturition resulting in the delivery of a newborn is a fundamental event ensuring survival of the species. In humans, the main clinical problems of parturition include activation of the process too early or too late resulting in the delivery of pre-term and post-term infants, both with their own implications for future health for the mother and baby. Additionally, where parturition systems are not activated correctly, dysfunctional labour with the resulting need for caesarean delivery (CS), in addition to atonic post-partum haemorrhage can also ensue. Overall, in the UK up to 40% of pregnancies are affected by one of these problems. However, the exact processes involved in the initiation and maintenance of parturition in the human are not fully understood. With such an important event, influences are most likely to be multi-factorial, with hormonal, mechanical, inflammatory, biochemical and maternal environmental factors playing a part. The aims of this thesis were to investigate influences on parturition in human pregnancy. Firstly, the myometrial transcriptional effects of long term exposure to the uterotonic oxytocin (OT) were examined. Further investigation of the myometrial and maternal peripheral response to uterine contractions in-vitro and in-vivo was also made with particular reference to the role of inflammation and myocyte damage. Additionally, the influence of maternal factors, particularly obesity, on the myometrial in-vitro contractile function and response to OT was studied. Initially, 150 gene arrays were produced using the Illumina platform. The samples were derived from myometrium taken at pre-labour CS which subsequently underwent functional contractility experiments in an organ bath. Five drug environments were studied, namely OT, acetic acid (OT vehicle), ML7(a tocolytic acting via inhibition of myosin light chain kinase), ML7 & OT and finally DMSO (ML7 vehicle). Additionally, five time-points of 0, 1, 2, 4, and 6 hours after drug addition were used, resulting in 5 samples for each drug and time combination. The results indicated that despite a clear enhancement of myometrial contractile activity by OT, this functional response does not appear to be mediated by cellular transcription. However, there was a clear contraction and time dependent transcriptional wave, with overrepresentation of genes associated with inflammation and cellular damage/apoptosis, and down-regulation of pathways concerning cellular metabolism. These findings were confirmed by QPCR on further myometrial samples undergoing additional in-vitro functional studies. In addition to the temporal and contractile association with the inflammatory response, our data suggest inflammation occurs in response to myocyte cellular damage regardless of mode of damage e.g. contractile or chemically induced. This was demonstrated by inflammatory upregulation in myometrium exposed to the tocolytic agents nifedipine and ritodrine, which is not seen in response to ML7. Additionally, the myometrial inflammatory response was enhanced by the infective agent LPS. However, contrary to other proposals, the enhanced inflammatory response of the myometrium did not alter or promote the in-vitro contractile ability of the myometrium or its response to OT. This myometrial transcriptional data therefore suggests that the inflammatory response of labour is associated with contraction, chemical or infection induced myometrial cellular damage, but would not be considered necessary for a contractile response. Our in-vivo study of peripheral changes in the maternal circulation again supported our in-vitro myometrial data. Data showed that the effect of pregnancy at term was limited to increased white cell count driven by a neutrophilia, with no suggestion of leukocyte priming prior to labour. Additionally, term pregnancy is associated with an increase in CRP, an increase in GCSF (corresponding with the neutrophilia) in addition to suppression of the chemokines CCL11 and CCL22. Subsequently, we found that repeated blood samples taken at 2 hourly intervals during term labour induced dramatic changes in inflammatory cells and inflammatory mediators in the maternal circulation. Importantly, these changes occur in a co-ordinated time and contraction dependent manner, with the degree of inflammation associated with the length of time in labour and the degree of myocyte damage as measured by circulating CK and Mb. Our study of the influence of maternal factors on myometrial contractile ability and response to OT examined in-vitro myometrial contractility of 609 myometrial strips from 85 women. We demonstrated that maternal obesity does not impair spontaneous or OT induced myometrial contractions in-vitro. Furthermore, maternal age, ethnicity, parity, previous caesarean delivery,gestation at delivery and birthweight do not influence in-vitro myometrial spontaneous or OT induced contractile activity. This therefore suggests that the observed implication of these maternal and infant factors on parturition in-vivo (high rates of induction of labour, high rates of intrapartum caesarean delivery and post partum haemorrhage) cannot be explained by an effect on myometrial contraction per se. This therefore merits further investigation as to alternative mechanisms to ultimately promote and effective, uncomplicated and safe labour and vaginal delivery for at risk mothers. In summary, this thesis provides evidence that the myometrial contractions of human labour, whether spontaneous or OT induced are capable of inducing a temporal wave of transcriptional changes associated with the processes of inflammation, cellular damage/apoptosis with inhibition of cellular metabolic processes. In addition, maternal peripheral circulating factors mirror the myometrial transcriptional changes. These changes are highly comparable with those seen in response to exercising skeletal muscle, and in this model have been shown to play an important role in muscle repair and remodelling after exercise. Therefore, we would suggest that the inflammatory reaction typically associated with human labour occurs as a non-specific response to contraction induced cellular damage and may play a role in postpartum repair and remodelling of the uterus

Mute force and ignorance : incivility and gender in Scotland

This article considers the complex relationship between civility and gender in Scottish politics. It addresses two themes that have dominated discussion of Scotland's political tone. The first has been the seeming rise in intemperate political discourse, amplified by social media and the divisiveness of Scottish independence. The second has been those developments in the representation of gender in Scottish politics, both in the composition of the Scottish Parliament and in discourses around First Minister, Nicola Sturgeon. We also focus in on discourses surrounding a recent breach of civility by male Liberal Democrat MSP, Alex Cole-Hamilton, in which Cole-Hamilton is recorded mouthing an expletive towards a female Scottish government minister during a Zoom meeting of the Scottish Parliament's Equalities and Human Rights Committee on 11 February 2021. Analysis of this includes political responses to the ‘outburst’ and its subsequent media coverage, and examines, in particular, associations with masculinity and the relevance of the mitigating pleas of exasperated spontaneity. The article makes broader associations between the representation of this example of political incivility and those asymmetrical gender power relations given prominence by the #MeToo movement. Drawing on literature about angry populism, the article draws lessons about how mainstream politicians weaponise the language of incivility

The mediated communication of gender and sexuality in contemporary politics : from equality of representation to the re-emergence of the masculine

This Special Issue arrives at a time of contradiction and challenge in the study of gender and politics. The strive to have the voices of those outside of the straight white male political order is one that has been the subject of political debate for over a century. From the 1970s onwards, equality came to be enshrined in law in many countries. Progressive politics has begun to internalise this drive for equality of representation, with political institutions such as the Nordic states and devolved parliaments of Wales and Scotland increasing the proportions of women elected to office. Male politicians have been encouraged to demonstrate their own acceptance of such equality issues. Yet, throughout political life, women still confront variations of the dilemma between the exercise of power and conventions of femininity commonly referred to as the “double bind”. In what has recently articulated as the “power paradox”, women are encouraged to pursue political office, but are routinely demeaned and treated with suspicion when they meet with success. Added to this is the rise of a new populism, laced with that toxic masculinity identified by some of our contributors, where gendered abuse has become a tactical resource in a grotesque lexicon of “authentic” expression

Ethnic differences in physical activity, diet and obesity - research findings

Research findings report of ETHNIC DIFFERENCES IN PHYSICAL ACTIVITY, DIET AND OBESITY project. A project in the ESRC Understanding Population Trends and Processes Programme, maintained by the ReStore repository and archived to NCRM Eprints 2022

The safeguarding capability of adults in Catholic Church ministries: A global perspective

Background: In the wake of historical sexual abuse across the Catholic Church globally, the Church continues to develop policies and processes to prevent and respond to child sexual abuse, including supporting the skills, knowledge, and confidence of members of the Church. Objective: We investigated the safeguarding capabilities of a range of people with different roles within Catholic Church ministries in various countries. Participants and setting: Our 184 participants included lay people, religious men and women, school staff, safeguarding officers and tertiary students associated with the Catholic Church. Data were collected across seven different countries. Methods: We measured the awareness, confidence, attitudes, and knowledge of participants and examined differences between participants in different roles within the Church and different countries through General Linear Models. Results: We found varying levels of awareness, confidence, attitudes, and knowledge regarding sexual abuse prevention and safeguarding. We pinpointed the significant differences in three of these domains (confidence, attitudes, and knowledge) both between people with different roles in the church worldwide, but also between the countries from which participants came from. Conclusions: We found that people in various countries and roles within the Church are at different stages of their safeguarding journey. Some are still understanding their roles (attitudes), some are still learning about how it is operationalised (awareness), and others are acquiring skills that will prepare them for enacting safeguarding policies and practices (confidence)

Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs)

Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells

Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients

Background: Interleukin 2 receptor antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute rejection in kidney transplant recipients. Use of IL2Ra has increased steadily, with 38% of new kidney transplant recipients in the United States, and 23% in Australasia receiving IL2Ra in 2002. Objectives: This study aims to systematically identify and summarise the effects of using an IL2Ra, as an addition to standard therapy, or as an alternative to other antibody therapy. Search strategy: The Cochrane Renal Group's specialised register (June 2003), the Cochrane Controlled Trials Register (in The Cochrane Library issue 3, 2002), MEDLINE (1966-November 2002) and EMBASE (1980-November 2002). Reference lists and abstracts of conference proceedings and scientific meetings were hand-searched from 1998-2003. Trial groups, authors of included reports and drug manufacturers were contacted. Selection criteria: Randomised controlled trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or other antibody therapy. Data collection and analysis: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) with 95% confidence intervals (CI). Main results: One hundred and seventeen reports from 38 trials involving 4893 participants were included. Where IL2Ra were compared with placebo (17 trials; 2786 patients), graft loss was not significantly different at one (RR 0.83, 95% CI 0.66 to 1.04) or three years (RR 0.88, 95% CI 0.64 to 1.22). Acute rejection (AR) was significantly reduced at six months (RR 0.66, 95% CI 0.59 to 0.74) and at one year (RR 0.67, 95% CI 0.60 to 0.75). At one year, cytomegalovirus (CMV) infection (RR 0.82, 95% CI 0.65 to 1.03) and malignancy (RR 0.67, 95% CI 0.33 to 1.36) were not significantly different. Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but adverse effects strongly favoured IL2Ra. Reviewer's conclusions: Given a 40% risk of rejection, seven patients would need treatment with IL2Ra to prevent one patient having rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effect