TRPV4 activation triggers the release of melatonin from human non-pigmented ciliary epithelial cells

Melatonin is a neurohormone mainly produced in the pineal gland; nevertheless, various ocular structures such as the ciliary body, lens and the retina produce it. One of the roles of melatonin in the eye is the modulation of intraocular pressure, although little is known about the mechanisms that causes its presence in the aqueous humour. TRPV4 is a membrane channel which is activated by both physical and chemical stimuli. Therefore, this channel is sensitive to osmotic and hydrostatic pressure. As a consequence, TRPV4 results as an interesting candidate to study the relation between the activation of the TRPV4 channel and the production of melatonin. In this sense we have studied the role of the TRPV4 agonist GSK1016790A to modulate the production of melatonin in a cell line derived from human non-pigmented ciliary epithelial cells. The stimulation of the TRPV4 produced an increase in the extracellular melatonin levels changing from 8.5 ± 0.6 nM/well/30 min (control) to 23.3 ± 2.1 nM/well/30 min after 10 nM GSK1016790A application, this action being blocked by the selective antagonist RN 1734. The activation of the TRPV4 by GSK1016790A permitted to observe a melatonin increase which was concentration-dependent, and provided a pD2 value of −8.5 ± 0.1 (EC50 of 3.0 nM). In conclusion, the activation of the TRPV4 present in human non-pigmented ciliary epithelial cells can modulate the presence of extracellular melatonin, this being of relevance since this substance controls the dynamics of the aqueous humour.

Short-term secular change in height, body mass and Tanner-Whitehouse 3 skeletal maturity of Madeira youth, Portugal

Secular trends in height and weight are reasonably well documented in Europe. Corresponding observations for skeletal maturation are lacking. Aim: To assess secular trends in height, body mass and skeletal maturity of Portuguese children and adolescents and to provide updated reference values for skeletal maturity scores (SMSs). Subjects and methods: Data for 2856 children and adolescents of 4–17 years, 1412 boys and 1444 girls, from The ‘Madeira Growth Study’ (MGS; 1996–1998) and from the‘Healthy Growth of Madeira Children Study’ (CRES; 2006) were used. Height and body mass were measured. Skeletal maturity was assessed with the Tanner-Whitehouse 2 and 3 methods. Results: Children from CRES were taller and heavier than peers from MGS. Differences in height reached 5.8cm in boys and 5.5cm in girls. RUS SMSs did not differ consistently between surveys boys, while higher RUS scores were observed in CRES girls. Adult RUS SMSs for MGS and CRES combined were attained at 15.8 years in boys and 14.8 years in girls. Corresponding ages for adult Carpal SMSs were 14.4 and 14.0, respectively. Conclusion: The short-term trends for height and mass were not entirely consistent with the trends in RUS and Carpal SMSs and SAs.

Robustness of the Estuarine Fish Assessment Index (EFAI) regarding water body definition criteria

According to the Water Framework Directive (WFD) transitional waters should be differentiated according to type and, in some cases, divided into different water bodies. This raises a dilemma in trying to define parts of a continuum. In the sequence of WFD several indices have been proposed including the Estuarine Fish Assessment Index, which can be applied taking an estuary as a whole (EFAI - without water bodies division) or divided in water bodies (EFAI(WB)). The purpose of this work is to analyze the robustness of the Estuarine Fish Assessment Index, based on three different ways of dividing Portuguese estuaries into water bodies according to different criteria (criterion 1 - distance to the estuary mouth, criterion 2 - salinity and criterion 3 - morphology, salinity and human dimension as pressure and state). In this study we evaluated at which degree these three criteria could influence the ecological quality ratio (EQR) results, when the index was applied to water body level (EFAI(WB)). Also, for each estuary, the EQR(WB) results for each criterion of EFAI(WB) were combined and weighted according to the water bodies areas (EFAI overall weighted - EFAI(Ow)). Finally, it was compared if the results obtained for each criterion with the EFAI(OW) were similar to the results of the index application taking the estuary as a whole (EFAI without water bodies division). No significant differences were found in both cases, which indicated that this index is a robust method regarding the division of the estuaries in different water bodies, which is an important element of a fish-based multimetric tool for assessing estuarine ecological quality. However, in some cases, different ecological quality statuses were achieved when applying the EFAI(Ow) or the EFAI. This work addressed several aspects regarding the possible division of water bodies at the WFD context. (C) 2012 Elsevier Ltd. All rights reserved.

Re-imagining the theology of human sexuality in the Methodist Church: the use of narrative in theological methodology

This thesis proposes the development of a narrative methodology in the British Methodist Church. Such a methodology embraces and communicates both felt experience and critical theological thinking, thus producing and presenting a theology that might have a constructive transformative impact on wider society. In chapter one I explore the ways in which the Church speaks in public, identify some of the challenges it faces, and consider four models of engagement. If the Church is to engage in public discourses then I argue that its words need to be relevant and connect with people’s experiences. To ground the thinking I focus on the context of the British Methodist Church and explore how the Church engages in theological reflection through the lens of its thinking on issues of human sexuality. Chapter two reviews how theological reflection is undertaken in the British Methodist Church. I describe how the Methodist Quadrilateral of Scripture, tradition, reason and experience remains a foundational framework for theological reflection within the Methodist Church and consider the impact of institutional processes and the ways in which the Methodist people actually engage with theological thinking. The third and fourth chapters focus on how the British Methodist Church has produced its theology of human sexuality, giving particular attention to the use of personal and sexual stories in this process. I find that whilst there has been a desire to listen to the stories of the Methodist people, there has not been a corresponding interrogation or analysis of their stories so as to enable robust and constructive theological reflection on these experiences. Using resources from Foucauldian approaches to discourse analysis, I critique key statements and the processes involved in their production, offering an analysis of this body of theological thinking and indicating where possibilities for alternative ways of thinking and acting arise. The proposed methodology draws upon resources from social science methodologies, and in chapter five I look at the use of personal experience and relevant strategies of inquiry that prompt reflection on the hermeneutical process and employ narrative approaches in undertaking, analysing and presenting research. The exploration shows that qualitative research methodologies offer resources and methods of inquiry that could help the Church to engage with personal stories in its theological thinking in a robust, interrogative and imaginative way. In chapter six an examination of story and narrative is undertaken, to show how they have been understood as ways of knowing and how they relate to theological inquiry. Whilst acknowledging some of the limitations of narrative, I indicate how it offers constructive possibilities for theological reflection and could be a means for the British Methodist Church to engage in public discourse. This is explored further in chapter seven, which looks in more detail at how the British Methodist Church has used narrative in its theological thinking, and outlines areas requiring further attention in order for a narrative theological methodology to be developed, namely: attention to the question ‘whose experience?’; investigation of issues of power and the dynamics involved in the process of the production of theological thought; how personal stories and experiences are interrogated and how narrative is constructed; and how narrative might be employed within the Methodist Quadrilateral. The final chapter considers the advantages and limitations of such an approach, whether the development of such a method is possible in the Methodist Church today and its potential for helping the Church to engage in public discourse more effectively. I argue that this methodology can provoke new theological insights and enable new ways of being in the world

Short-term secular change in height, body mass and Tanner-Whitehouse 3 skeletal maturity of Madeira youth, Portugal

Secular trends in height and weight are reasonably well documented in Europe. Corresponding observations for skeletal maturation are lacking. Aim: To assess secular trends in height, body mass and skeletal maturity of Portuguese children and adolescents and to provide updated reference values for skeletal maturity scores (SMSs). Subjects and methods: Data for 2856 children and adolescents of 4–17 years, 1412 boys and 1444 girls, from The ‘Madeira Growth Study’ (MGS; 1996–1998) and from the‘Healthy Growth of Madeira Children Study’ (CRES; 2006) were used. Height and body mass were measured. Skeletal maturity was assessed with the Tanner-Whitehouse 2 and 3 methods. Results: Children from CRES were taller and heavier than peers from MGS. Differences in height reached 5.8cm in boys and 5.5cm in girls. RUS SMSs did not differ consistently between surveys boys, while higher RUS scores were observed in CRES girls. Adult RUS SMSs for MGS and CRES combined were attained at 15.8 years in boys and 14.8 years in girls. Corresponding ages for adult Carpal SMSs were 14.4 and 14.0, respectively. Conclusion: The short-term trends for height and mass were not entirely consistent with the trends in RUS and Carpal SMSs and SAs.

“Biomarkers in a One Health perspective: current knowledge of their ability to merge human and animal health

Biomarkers are nowadays essential tools to be one step ahead for fighting disease, enabling an enhanced focus on disease prevention and on the probability of its occurrence. Research in a multidisciplinary approach has been an important step towards the repeated discovery of new biomarkers. Biomarkers are defined as biochemical measurable indicators of the presence of disease or as indicators for monitoring disease progression. Currently, biomarkers have been used in several domains such as oncology, neurology, cardiovascular, inflammatory and respiratory disease, and several endocrinopathies. Bridging biomarkers in a One Health perspective has been proven useful in almost all of these domains. In oncology, humans and animals are found to be subject to the same environmental and genetic predisposing factors: examples include the existence of mutations in BR-CA1 gene predisposing to breast cancer, both in human and dogs, with increased prevalence in certain dog breeds and human ethnic groups. Also, breast feeding frequency and duration has been related to a decreased risk of breast cancer in women and bitches. When it comes to infectious diseases, this parallelism is prone to be even more important, for as much as 75% of all emerging diseases are believed to be zoonotic. Examples of successful use of biomarkers have been found in several zoonotic diseases such as Ebola, dengue, leptospirosis or West Nile virus infections. Acute Phase Proteins (APPs) have been used for quite some time as biomarkers of inflammatory conditions. These have been used in human health but also in the veterinary field such as in mastitis evaluation and PRRS (porcine respiratory and reproductive syndrome) diagnosis. Advantages rely on the fact that these biomarkers can be much easier to assess than other conventional disease diagnostic approaches (example: measured in easy to collect saliva samples). Another domain in which biomarkers have been essential is food safety: the possibility to measure exposure to chemical contaminants or other biohazards present in the food chain, which are sometimes analytical challenges due to their low bioavailability in body fluids, is nowadays a major breakthrough. Finally, biomarkers are considered the key to provide more personalized therapies, with more efficient outcomes and fewer side effects. This approach is expected to be the correct path to follow also in veterinary medicine, in the near future.

The Expanded Human Kallikrein (KLK) gene family : genomic organisation, tissue specific expression and potential functions

The tissue kallikreins are serine proteases encoded by highly conserved multigene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13 26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5 or 3 untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25–44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.