Molecular Genetic Studies of Melanocortin Receptors in Morbid Obesity

The prevalence of obesity is increasing at an alarming rate in all age groups worldwide. Obesity is a serious health problem due to increased risk of morbidity and mortality. Although environmental factors play a major role in the development of obesity, the identification of rare monogenic defects in human genes have confirmed that obesity has a strong genetic component. Mutations have been identified in genes encoding proteins of the leptin-melanocortin signaling system, which has an important role in the regulation of appetite and energy balance. The present study aimed at identifying mutations and genetic variations in the melanocortin receptors 2-5 and other genes active on the same signaling pathway accounting for severe early-onset obesity in children and morbid obesity in adults. The main achievement of this thesis was the identification of melanocortin-4 receptor (MC4R) mutations in Finnish patients. Six pathogenic MC4R mutations (308delT, P299H, two S127L and two -439delGC mutations) were identified, corresponding to a prevalence of 3% in severe early-onset obesity. No obesity causing MC4R mutations were found among patients with adult-onset morbid obesity. The MC4R 308delT deletion is predicted to result in a grossly truncated nonfunctional receptor of only 107 amino acids. The C-terminal residues, which are important in MC4R cell surface targeting, are totally absent from the mutant 308delT receptor. In vitro functional studies supported a pathogenic role for the S127L mutation since agonist induced signaling of the receptor was impaired. Cell membrane localization of the S127L receptor did not differ from that of the wild-type receptor, confirming that impaired function of the S127L receptor was due to reduced signaling properties. The P299H mutation leads to intracellular retention of the receptor. The -439delGC deletion is situated at a potential nescient helix-loop-helix 2 (NHLH2) -binding site in the MC4R promoter. It was demonstrated that the transcription factor NHLH2 binds to the consensus sequence at the -439delGC site in vitro, possibly resulting in altered promoter activity. Several genetic variants were identified in the melanocortin-3 receptor (MC3R) and pro-opiomelanocortin (POMC) genes. These polymorphisms do not explain morbid obesity, but the results indicate that some of these genetic variations may be modifying factors in obesity, resulting in subtle changes in obesity-related traits. A risk haplotype for obesity was identified in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene through a candidate gene single nucleotide polymorphism (SNP) genotyping approach. An ENPP1 haplotype, composed of SNPs rs1800949 and rs943003, was shown to be significantly associated with morbid obesity in adults. Accordingly, the MC3R, POMC and ENPP1 genes represent examples of susceptibility genes in which genetic variants predispose to obesity. In conclusion, pathogenic mutations in the MC4R gene were shown to account for 3% of cases with severe early-onset obesity in Finland. This is in line with results from other populations demonstrating that mutations in the MC4R gene underlie 1-6% of morbid obesity worldwide. MC4R deficiency thus represents the most common monogenic defect causing human obesity reported so far. The severity of the MC4-receptor defect appears to be associated with time of onset and the degree of obesity. Classification of MC4R mutations may provide a useful tool when predicting the outcome of the disease. In addition, several other genetic variants conferring susceptibility to obesity were detected in the MC3R, MC4R, POMC and ENPP1 genes.

Problem-based learning in an e-learning environment: A case study at Griffith University School of Medicine

Increasing numbers of medical schools in Australia and overseas have moved away from didactic teaching methodologies and embraced problem-based learning (PBL) to improve clinical reasoning skills and communication skills as well as to encourage self-directed lifelong learning. In January 2005, the first cohort of students entered the new MBBS program at the Griffith University School of Medicine, Gold Coast, to embark upon an exciting, fully integrated curriculum using PBL, combining electronic delivery, communication and evaluation systems incorporating cognitive principles that underpin the PBL process. This chapter examines the educational philosophies and design of the e-learning environment underpinning the processes developed to deliver, monitor and evaluate the curriculum. Key initiatives taken to promote student engagement and innovative and distinctive approaches to student learning at Griffith promoted within the conceptual model for the curriculum are (a) Student engagement, (b) Pastoral care, (c) Staff engagement, (d) Monitoring and (e) Curriculum/Program Review. © 2007 Springer-Verlag Berlin Heidelberg.

Regulating Food Consumption : Studies of change and variation in Europe

The role of people as buyers and eaters of food has changed significantly. From being protected by a paternalistic welfare state, people appear to be accorded more freedom and responsibility as individuals, where attention is redirected from the state towards market relations. Many have asserted that these changes are accompanied by fragmentation, individualisation, and privatisation, leading to individual uncertainty and lack of confidence. But empirical observations do not always confirm this, distrust is not necessarily growing and while responsibilities may change, the state still plays an active role. This dissertation explores changing relationships between states and markets, on the one hand, and ordinary people in their capacities as consumers and citizens, on the other. Do we see the emergence of new forms of regulation of food consumption? If so, what is the scope and what are the characteristics? Theories of regulation addressing questions about individualisation and self-governance are combined with a conceptualisation of consumption as processes of institutionalisation, involving daily routines, the division of labour between production and consumption, and the institutional field in which consumption is embedded. The analyses focus on the involvement of the state, food producers and scientific, first of all nutritional, expertise in regulating consumption, and on popular responses. Two periods come out as important, first when the ideas of “designing the good life” emerged, giving the state a very particular role in regulating food consumption, and, second, when this “designing” is replaced by ideas of choice and individual responsibility. One might say that “consumer choice” has become a mode of regulation. I use mainly historical studies from Norway to analyse the shifting role of the state in regulating food consumption, complemented with population surveys from six European countries to study how modernisation processes are associated with trust. The studies find that changing regulation is not only a question of societal or state vs individual responsibilities. Degrees of organisation and formalisation are important as well. While increasing organisation may represent discipline and abuses of power (including exploitation of consumer loyalty), organisation can also, to the consumer, provide higher predictability, systems to deal with malfeasance, and efficiency which may provide conditions for acting. The welfare state and the neo-liberal state have very different types of solutions. The welfare state solution is based on (national) egalitarianism, paternalism and discipline (of the market as well as households). Such solutions are still prominent in Norway. Individualisation and self-regulation may represent a regulatory response not only to a declining legitimacy of this kind of interventionism, but also increasing organisational complexity. This is reflected in large-scale re-regulation of markets as well as in relationships with households and consumers. Individualisation of responsibility is to the consumer not a matter of the number of choices that are presented on the shelves, but how choice as a form of consumer based involvement is institutionalised. It is recognition of people as “end-consumers”, as social actors, with systems of empowerment politically as well as via the provisioning system. ‘Consumer choice’ as a regulatory strategy includes not only communicative efforts to make people into “choosing consumers”, but also the provision of institutions which recognise consumer interests and agency. When this is lacking we find distrust as representing powerlessness. Individual responsibility-taking represents agency and is not always a matter of loyal support to shared goals, but involves protest and creativity. More informal (‘communitarian’) innovations may be an indication of that, where self-realisation is intimately combined with responsibility for social problems. But as solutions to counteract existing imbalances of power in the food market the impacts of such initiatives are probably more as part of consumer mobilisation and politicisation than as alternative provisioning.

Studies of the Human Transcriptome

Gene expression is one of the most critical factors influencing the phenotype of a cell. As a result of several technological advances, measuring gene expression levels has become one of the most common molecular biological measurements to study the behaviour of cells. The scientific community has produced enormous and constantly increasing collection of gene expression data from various human cells both from healthy and pathological conditions. However, while each of these studies is informative and enlighting in its own context and research setup, diverging methods and terminologies make it very challenging to integrate existing gene expression data to a more comprehensive view of human transcriptome function. On the other hand, bioinformatic science advances only through data integration and synthesis. The aim of this study was to develop biological and mathematical methods to overcome these challenges and to construct an integrated database of human transcriptome as well as to demonstrate its usage. Methods developed in this study can be divided in two distinct parts. First, the biological and medical annotation of the existing gene expression measurements needed to be encoded by systematic vocabularies. There was no single existing biomedical ontology or vocabulary suitable for this purpose. Thus, new annotation terminology was developed as a part of this work. Second part was to develop mathematical methods correcting the noise and systematic differences/errors in the data caused by various array generations. Additionally, there was a need to develop suitable computational methods for sample collection and archiving, unique sample identification, database structures, data retrieval and visualization. Bioinformatic methods were developed to analyze gene expression levels and putative functional associations of human genes by using the integrated gene expression data. Also a method to interpret individual gene expression profiles across all the healthy and pathological tissues of the reference database was developed. As a result of this work 9783 human gene expression samples measured by Affymetrix microarrays were integrated to form a unique human transcriptome resource GeneSapiens. This makes it possible to analyse expression levels of 17330 genes across 175 types of healthy and pathological human tissues. Application of this resource to interpret individual gene expression measurements allowed identification of tissue of origin with 92.0% accuracy among 44 healthy tissue types. Systematic analysis of transcriptional activity levels of 459 kinase genes was performed across 44 healthy and 55 pathological tissue types and a genome wide analysis of kinase gene co-expression networks was done. This analysis revealed biologically and medically interesting data on putative kinase gene functions in health and disease. Finally, we developed a method for alignment of gene expression profiles (AGEP) to perform analysis for individual patient samples to pinpoint gene- and pathway-specific changes in the test sample in relation to the reference transcriptome database. We also showed how large-scale gene expression data resources can be used to quantitatively characterize changes in the transcriptomic program of differentiating stem cells. Taken together, these studies indicate the power of systematic bioinformatic analyses to infer biological and medical insights from existing published datasets as well as to facilitate the interpretation of new molecular profiling data from individual patients.

Science as a hobby: how and why I came to study the social life of an Indian primitively eusocial wasp

For the most part, my research career has involved prying into the life of the locally abundant primitively eusocial paper wasp, Ropalidia marginata, with the aim of understanding the origin and evolution of social life in insects. My interest in this wasp species began as a hobby, but I was privileged to soon convert my hobby into my profession. Here I describe how this conversion came about, what it meant to pursue my hobby as a full-time activity, describe some examples from my research and end with some reflections about the process of doing modern science, especially in India.

Corporate social responsibilities of Indian public sector enterprises-a case study of Bharat Heavy Electricals Limited (BHEL)

The high level of public accountability attached to Public Sector Enterprises as a result of public ownership makes them socially responsible. The Committee of Public Undertakings in 1992 examined the issue relating to social obligations of Central Public Sector Enterprises and observed that ``being part of the `State', every Public Sector enterprise has a moral responsibility to play an active role in discharging the social obligations endowed on a welfare state, subject to the financial health of the enterprise''. It issued the Corporate Social Responsibility Guidelines in 2010 where all Central Public Enterprises, through a Board Resolution, are mandated to create a CSR budget as a specified percentage of net profit of the previous year. This paper examines the CSR activities of the biggest engineering public sector organization in India, Bharath Heavy Electricals Limited. The objectives are twofold, one, to develop a case study of the organization about the funds allocated and utilized for various CSR activities, and two, to examine its status with regard to other organizations, the 2010 guidelines, and the local socio-economic development. Secondary data analysis results show three interesting trends. One, it reveals increasing organizational social orientation with the formal guidelines in place. Two, Firms can no longer continue to exploit environmental resources and escape from their responsibilities by acting separate entities regardless of the interest of the society and Three the thrust of CSR in public sector is on inclusive growth, sustainable development and capacity building with due attention to the socio-economic needs of the neglected and marginalized sections of the society.

Folivory as a Constraint on Social Behaviour of Langurs in South India

Folivory, being a dietary constraint, can affect the social time of colobines. In the present study, we compared food items and activity budgets of two closely related species of colobines inhabiting South India, i.e. the Hanuman langur (Semnopithecus hypoleucos) and Nilgiri langur (Semnopithecus johnii), to determine whether folivory had an impact on social time in these species. Our study established that Nilgiri langurs were more folivorous than Hanuman langurs. Nilgiri langurs spent much less time on social activities, but more time on resting, although the social organization of S. hypoleucos was similar to that of the Nilgiri langur. The enforced resting time for fermentation of leafy food items may have reduced the time available for social interactions, which in turn affected the social time in Nilgiri langurs. By comparing the data from previous studies on other Hanuman langur species, we found that S. hypoleucos spent a similar amount of time on social activities as Semnopithecus entellus. Hence, the social behaviour of S. entellus and S. hypoleucos is phylogenetically highly conservative. (C) 2015 S. Karger AG, Basel

The India MPA Workshop Proceedings. Social Dimensions of Marine Protected Areas Implementation in India: do Fishing Communities Benefit? 21-22 January 2009, IMAGE Auditorium, Chennai, India

In the current context of natural resource management, marine protected areas (MPAs) are being widely propagated as an important tool for the conservation of marine and fisheries resources. The International Collective in Support of Fishworkers (ICSF) recently undertook a series of studies on MPAs in India to highlight the various legal, institutional, policy and livelihoods issues that confront fishing and coastal communities. In order to discuss the findings of these case studies and to suggest proposals for livelihood-sensitive conservation and management of coastal and fisheries resources through participatory processes, ICSF organized a two-day workshop on ‘Social Dimensions of Marine Protected Area Implementation in India: Do Fishing Communities Benefit?’ at Chennai on 21-22 January 2009. This publication—the India MPA Workshop Proceedings—contains the prospectus of the workshop, a report of the proceedings and the consensus statement that was reached by organizations and individuals who particapated in the workshop. This publication will be useful for fishworkers, non-governmental organizations, policymakers, trade unions, researchers and others interested in natural resource management and coastal and fishing communities.

Mapping social change in U.S. coastal counties: a social atlas of coastal North Carolina

This document represents a pilot effort to map social change in the coastal United States—a social atlas characterizing changing population, demographic, housing, and economic attributes. This pilot effort focuses on coastal North Carolina. The impetus for this project came from numerous discussions about the usefulness and need for a graphic representation of social change information for U.S. coastal regions. Although the information presented here will be of interest to a broad segment of the coastal community and general public, the intended target audience is coastal natural resource management professionals, Sea Grant Extension staff, urban and regional land-use planners, environmental educators, and other allied constituents interested in the social aspects of how the nation’s coasts are changing. This document has three sections. The first section provides background information about the project. The second section features descriptions of social indicators and depictions of social indicator data for 1970, 1980, 1990, and 2000, and changes from 1970 to 2000 for all North Carolina coastal counties. The third section contains three case studies describing changes in select social attributes for subsets of counties. (PDF contains 67 pages)

Heritage interpretation challenges and management issues at film-induced tourism heritage attractions: Case studies of Rosslyn Chapel and Alnwick Castle

Although previous research has widely acknowledged the phenomenon of film-induced tourism, there is a paucity of research in relation to management of film-induced tourism at built heritage sites. This research, underpinned by a constructivist paradigm, draws on three distinct fields of study – heritage tourism management, film-induced tourism and heritage interpretation – in order to provide a contribution to the heritage management field and address this particular gap in knowledge. Relying on the method of semi-structured interviews with managers, guides and visitors at Rosslyn Chapel (RC) and Alnwick Castle (AC), this thesis provides a rich understanding of how heritage interpretation can address a range of management challenges at heritage sites where film-induced tourism has occurred. These heritage visitor attractions (HVAs) were specifically selected as case studies as they have played different roles in media products. Rosslyn Chapel (RC) was an actual place named in The Da Vinci Code (TDVC) book and then film, whereas Alnwick Castle (AC) served as a backdrop for the first two Harry Potter (HP) films. Findings of this research include a range of management challenges at both RC and AC such as an increase in visitor numbers; seasonality issues; changes in visitor profile; revenue generation concerns; conservation, access, and visitor experience; and the complex relationship between heritage management and tourism activities. The findings also reveal film-induced tourism’s implications for heritage interpretation such as the various visitors’ expectations for heritage interpretation, changes to heritage interpretation as a result of film-induced tourism, and issues with commodification. These findings also demonstrate that film-induced tourism to some extent influenced visitors’ preferences for heritage interpretation, though visitors’ preferences differed from one to another. This thesis argues that, in the context of film-induced tourism at HVAs, as evident from the two case studies considered, heritage interpretation can be a valuable management tool and can also play a significant role in the quality of the visitors’ experience.

Critical incident technique and explicitation interviewing in studies of information behavior

Urquhart, C., Light, A., Thomas, R., Barker, A., Yeoman, A., Cooper, J., Armstrong, C., Fenton, R., Lonsdale, R. & Spink, S. (2003). Critical incident technique and explicitation interviewing in studies of information behavior. Library and Information Science Research, 25(1), 63-88. Sponsorship: JISC (for JUSTEIS element)

Fractionation and compositional studies of rabbit skeletal muscle membranes

The observations of Hooke (1665), Schleiden & Schwann (1839) and Virchow (1855) led to the identification of the cell as the basic structural unit of living material. In the intervening years, it has been firmly established that the chemical processes which underlie the proper functioning, development and reproduction of the organism are cellular activities. The development of the electron microscope has enabled cell structure to be studied in detail. A picture of the cell as an entity with a complex and highly organised internal structure has emerged from the work of Palade, Porter, Fernandez-Moran and many others. Although cells from different tissues and organisms differ in aspects of their structure and consequently in function, they have several features in common. A retentive membrane encloses a number of cell constituents, which include membrane-enclosed subcellular structures known as organelles. The cells of most tissues also contain a reticulum or system of branching tubules. The interplay of the biochemical activities of these structures enables the cell to function. Almost thirty years ago, Claude, Palade, Schneider, Hogeboom, de Duve and others set out to analytically fractionate the subcellular components obtained after the fragmentation of liver cells. This approach has become known as subcellular fractionation, and signalled a major conceptual breakthrough in biochemistry (reviewed by de Duve, 1964, 1967, 1971). The significance of this breakthrough has been underlined by the award of the 1974 Nobel Prize in Medicine to de Duve, Palade and Claude. This thesis is concerned with the application of subcellular fractionation techniques to the separation and characterisation of the membrane systems of the rabbit skeletal muscle cell.