Regulation of IL-4 mediated signalling in primary human bronchial fibroblasts by IL-13Rα2

Fibroblasts are key effector cells involved in airway inflammation and remodelling in asthma. Interleukin (IL)-4 and IL-13 are important cytokines in the asthma phenotype which act on fibroblasts and other cell types. These cytokines exhibit overlapping functions through use of a common receptor, IL-4Rα:IL-13Rα1. Another receptor, IL 13 Receptor α2 (IL-13Rα2), originally thought to be a decoy receptor for IL-13, has recently been shown to attenuate responses to IL-4 as well as IL-13, by an unknown mechanism. In this thesis, I tested the hypothesis that IL-13Rα2 is responsible for the regulation of IL-4 mediated signalling in bronchial fibroblasts and that regulation by IL-13Rα2 is altered in asthma. The expression of IL-4 and IL-13 receptors on human bronchial fibroblasts (HBFs) was highly dynamic. IL-13Rα2 expression was significantly increased in response to both IL-4 and IL-13 over 24 hours, requiring de novo protein synthesis. A significant rapid reduction in IL-4Rα expression was also observed in response to either ligand, although levels rapidly returned to normal after removal of the stimulus. Use of a neutralizing antibody showed that induction of IL 13Rα2 suppressed STAT-6 activation and the pro-inflammatory effects of IL-4 and IL-13. No difference was observed in receptor expression levels or the regulatory effects of IL-13Rα2 between healthy and asthmatic subjects. IL-13Rα2 was also up-regulated by a range of Th1 stimuli including IFNγ and IFNβ, as well as double stranded RNA (dsRNA), with no disease-related differences. The up-regulation of IL 13Rα2 in response to dsRNA hampered attempts to knock down surface expression of IL-13Rα2 using siRNA, but revealed a potential role for IL-13Rα2 in the anti-viral response due to its ability to down-regulate responses to IL-4 and IL-13. An over expression model of IL-13Rα2 identified the potential for IL-4 to cause activation of STAT3 mediated by IL-13Rα2. In HBFs naturally expressing high levels of IL-13Rα2, addition of IL-4, but not IL-13, significantly increased activation of STAT3, a transcription factor associated with cell survival. Whilst IL-13Rα2 may have beneficial anti-inflammatory effects by suppressing STAT-6 mediated responses, further work is required to determine potential pro-fibrotic consequences of IL-4/IL-13Rα2 mediated STAT3 activation in HBFs. Since no difference was observed in IL-13Rα2 expression or in its anti-inflammatory efficacy in HBFs from normal or asthmatic donors, these data suggest that the atopic environment is more important than intrinsic differences in the ability of asthma-derived fibroblasts to respond to IL-4 and IL-13

An exercise in happiness: Physical activity choices and psychological wellbeing in post-partum mothers

Depression in the post-partum period affects a substantial number of mothers and can have serious consequences for quality of life and parenting. It is therefore imperative that the factors that can protect against and provide resilience to parental depression are identified. Exercise and physical activity has previously been found to be effective in decreasing symptoms of depression however the efficacy of exercise as an intervention is still unclear. Using a cross-sectional design and an opportunistic sample, this study sought to explore what exercise mothers choose to, or are able to, engage in and associations with depression and social support. Three-hundred and four mothers (mean age = 32.7 years) with young children (mean age = 14.2 months) completed an online questionnaire consisting of the Edinburgh Postnatal Depression Scale (EPNDS), Multidimensional Scale of Perceived Social Support (MSPSS) and questions on their physical activity choices (what type, how often, etc). Mothers were divided into groups based on their self-reported exercise habits: No exercise (N-E), own exercise (O-E) and mother-baby exercise classes (M-B). The results found that mothers who engaged in mother-baby exercise classes had significantly less depression symptomology. Frequency of attending classes was associated with social support, with higher scores on the measure of depression related to lower levels of social support (in total and separately from family, friends, and significant others). Not participating in any exercise was reported to be related to lack of childcare and time. These results suggest that, outside of targeted interventions, mother who seek out group exercise classes gain in social support, which may be protective against depression. Assisting mothers with opportunities to engage with such classes should be a priority

Captive Breeding and Reintroduction of Amphibians as a Conservation Tool. A thesis submitted for the degree of MSc in Biodiversity Management by Research

Recent figures show that over 30% of the world’s amphibian species are considered to be threatened with extinction. As the current escalation in extinctions continue the number of species going into captive breeding programmes is likely to increase. The Amphibian Conservation Action Plan (ACAP) states that captive assurance colonies are the only hope for species at immediate risk of extinction. This study reviewed current amphibian captive breeding and reintroduction programmes to identify increases in programmes and changes in terms of threats, geographical regions and species status since the publication of the ACAP in 2007. A 30% increase in conservation breeding programmes has been observed since the ACAP. A significant increase was seen in species within programmes in Latin America with more than 60% of the programmes identified being from South America, Central America and the Caribbean. The numbers of Least Concern species in captive programmes have declined since the ACAP, while Critically Endangered species increased by 20%. Habitat loss remained the largest threat to species within these programmes. These factors indicate that the ex situ recommendations made within the ACAP are beginning to influence the types of conservation methods being used to combat amphibian declines. Sixty-two amphibian reintroduction programmes were assessed against ten reintroduction criteria in order to understand how compliant they are with current guidelines. All species in programmes were of conservation importance locally, regionally or globally, so complied with the criterion relating to threats. However, fewer programmes met the criteria relating to the establishment of viable populations and adequate resources. Reintroduction programmes of longer duration and higher success were shown to meet reintroduction criteria more completely indicating that a programme needs to run for around 15 years or more in order to show a high level of success. Key measures to help ensure ex situ conservation is carried out for the right reasons and to the highest standard are identified. These include implementing conservation management through evidence-based theory and undertaking reintroductions in line with published criteria and recommendations. Keywords: translocation, amphibian decline, frog, toad, ex situ conservation, captive assurance, guidelines

An evaluation of Species Action Plans and factors influencing conservation reintroduction success

Through the Convention on Biological Diversity and the various approaches of governments and NGOs, Species Action Plans (SAPs) have become key in framing conservation action for threatened species. Despite their wide deployment in conservation, there have been no global comparative studies of SAP structure and content and how they are created, reviewed, and utilised. Species reintroductions often form a key part of SAPs and species recovery actions. Although species reintroductions are frequently assessed in terms of their outcomes, it is often unclear what 'success' or 'failure' mean and what factors might drive them. I aimed to establish (1) the key components and outputs of Species Action Plans, and how they compare across regions, taxa, and time; (2) how conservation practitioners utilise and perceive Species Action Plans; and (3) the factors that are influencing species reintroduction successes and failures. I did this by applying a mixed method approach utilising questionnaires and analysing case studies to establish practitioner perceptions, and patterns and relationships within the data. Results highlight the variation in SAP content across regions and time, finding that SAPs vary in structure and components across regions but less so across taxa, and that SAPs have evolved across time in line with scientific evidence, practice, and the associated development of guidance. Of note were the increased inclusion in recent years of success criteria and indicators, and that post-SAP reviews and evaluations were scarce and contained little information on SAP implementation or the success of actions in relation to indicators or monitoring. The development, value, utilization, and evaluation of SAPs was researched using data from an online questionnaire targeted at conservation practitioners. Conservation practitioners' perceptions of SAPs were positive, indicating that SAPs are highly valued and utilised widely. In relation to SAP content and structure, four principal components considered core to a SAP were identified. These were: (1) Strategic action and threats; (2) Species status; (3) Implementation, monitoring, and financial plans; and (4) Project vision. An evaluation of species reintroduction success was undertaken based on a global analysis of 341 case studies. It identified geographical and taxonomic variations in success rates and factors relating to partnerships and support, and habitat and release site as influential in success or failure. Having too many programme goals also appeared to be linked to a negative outcome. In summary, SAPs are extremely valuable but could be improved by having more focussed components that include priority actions, and separate implementation and monitoring plans. Having clear outcomes, measurable indicators or success criteria within SAPs and seeking practitioner feedback allows actions to be assessed and adapted. A stronger focus on partnerships and support, and habitat may improve reintroduction success

Mitigation-driven translocations: are we moving wildlife in the right direction?

Despite rapid growth in the field of reintroduction biology, many lessons learned from scientific research are not being applied to translocations initiated when human land-use conflicts with persistence of a species. Mitigation-driven translocations outnumber and receive better funding than science-based conservation translocations worldwide, yet their conservation benefit is unclear. As mitigation releases are economically motivated, outcomes may diverge greatly from releases designed to serve the biological needs of species. Translocation as a regulatory tool may be ill-fitted to biologically mitigate environmental damage wrought by development. Evidence suggests that many mitigation-driven translocations fail, though application of scientific principles and best-practices could likely increase success. Furthermore, lack of transparency and documentation of outcomes hinder efforts to understand the scope of the problem. If mitigation-driven translocations continue unabated as a part of the growing billion-dollar ecological consulting industry, it is imperative that the scale and effects of these releases are reported and evaluated

Global cities and cultural diversity: challenges and opportunities for young people’s nutrition.

Childhood obesity is a common concern across global cities and threatens sustainable urban development. Initiatives to improve nutrition and encourage physical exercise are promising but are yet to exert significant influence on prevention. Childhood obesity in London is associated with distinct ethnic and socio-economic patterns. Ethnic inequalities in health-related behaviour endure, underpinned by inequalities in employment, housing, access to welfare services, and discrimination. Addressing these growing concerns requires a clearer understanding of the socio-cultural, environmental and economic contexts of urban living that promote obesity. We explore opportunities for prevention using asset based-approaches to nutritional health and well-being, with a particular focus on adolescents from diverse ethnic backgrounds living in London. We focus on the important role that community engagement and multi-sectoral partnership play in improving the nutritional outcomes of London's children. London's children and adolescents grow up in the rich cultural mix of a global city where local streets are characterised by diversity in ethnicities, languages, religions, foods, and customs, creating complex and fluid identities. Growing up with such everyday diversity we argue can enhance the quality of life for London's children and strengthen their social capital. The Determinants of young Adult Social well-being and Health longitudinal study of about 6500 of London's young people demonstrated the positive impact of cultural diversity. Born to parents from over a hundred countries and exposed to multi-lingual households and religious practices, they demonstrated strong psychological resilience and sense of pride from cultural straddling, despite material disadvantage and discrimination. Supporting the potential contribution of such socio-cultural assets is in keeping with the values of social justice and equitable and sustainable development. Our work signals the importance of community engagement and multisectoral partnerships, involving, for example, schools and faith-based organisations, to improve the nutrition of London's children

Mental Distress among Young People in Inner-Cities:the Resilience, Ethnicity and AdolesCent Mental Health (REACH) study

BACKGROUND: Recent estimates suggest around 14% of 11–16 years in England have a mental health problem. However, we know very little about the extent and nature of mental health problems among diverse groups in densely populated inner cities, where contexts and experiences may differ from the national average. AIMS: To estimate the extent and nature of mental health problems in inner city London, overall and by social group, using data from our school-based accelerated cohort study of adolescent mental health, Resilience, Ethnicity and AdolesCent Mental Health. METHODS: Self-report data on mental health (general mental health, depression, anxiety, self-harm) were analysed (n, 4353; 11–14 years, 85% minority ethnic groups). Mixed models were used to estimate weighted prevalences and adjusted risks of each type of problem, overall and by gender, cohort, ethnic group and free school meals (FSM) status. RESULTS: The weighted prevalence of mental health problems was 18.6% (95% CI 16.4% to 20.8%). Each type of mental health problem was more common among girls compared with boys (adjusted risk ratios: mental health problems, 1.33, 95% CI 1.18 to 1.48; depression, 1.52, 1.30 to 1.73; anxiety, 2.09, 1.58 to 2.59, self-harm, 1.40, 1.06 to 1.75). Gender differences were more pronounced in older cohorts compared with the youngest. Mental health problems (1.28, 1.05 to 1.51) and self-harm (1.29, 1.02 to 1.56)—but not depression or anxiety—were more common among those receiving (vs not receiving) FSM. There were many similarities, with some variations, by ethnic group. CONCLUSIONS: Adolescent mental health problems and self-harm are common in inner city London. Gender differences in mental health problems may emerge during early adolescence

Association of time of breakfast and nighttime fasting duration with breast cancer risk in the multicase-control study in Spain

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer

Association of time of breakfast and nighttime fasting duration with breast cancer risk in the multicase-control study in Spain

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer

A flagship for Austral temperate forest conservation: an action plan for Darwin's frogs brings key stakeholders together

Darwin’s frogs Rhinoderma darwinii and Rhinoderma rufum are the only known species of amphibians in which males brood their offspring in their vocal sacs. We propose these frogs as flagship species for the conservation of the Austral temperate forests of Chile and Argentina. This recommendation forms part of the vision of the Binational Conservation Strategy for Darwin’s Frogs, which was launched in 2018. The strategy is a conservation initiative led by the IUCN SSC Amphibian Specialist Group, which in 2017 convened 30 governmental, non-profit and private organizations from Chile, Argentina and elsewhere. Darwin’s frogs are iconic examples of the global amphibian conservation crisis: R. rufum is categorized as Critically Endangered (Possibly Extinct) on the IUCN Red List, and R. darwinii as Endangered. Here we articulate the conservation planning process that led to the development of the conservation strategy for these species and present its main findings and recommendations. Using an evidence-based approach, the Binational Conservation Strategy for Darwin’s Frogs contains a comprehensive status review of Rhinoderma spp., including critical threat analyses, and proposes 39 prioritized conservation actions. Its goal is that by 2028, key information gaps on Rhinoderma spp. will be filled, the main threats to these species will be reduced, and financial, legal and societal support will have been achieved. The strategy is a multi-disciplinary, transnational endeavour aimed at ensuring the long-term viability of these unique frogs and their particular habitat