In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways

Visfatin is an adipogenic adipokine with increased levels in obesity, properties common to leptin. Thus, leptin may modulate visfatin production in adipose tissue (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3-L1 adipocytes and human/murine AT, with or without a leptin antagonist. The potential signaling pathways and mechanisms regulating visfatin production in AT was also studied. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. ELISA was performed to measure visfatin levels in conditioned media of AT explants, and small interfering RNA technology was used to reduce leptin receptor expression. Leptin significantly (P<0.01) increased visfatin levels in human and murine AT with a maximal response at leptin 10(-9) M, returning to baseline at leptin 10(-7) M. Importantly, ip leptin administration to C57BL/6 ob/ob mice further supported leptin-induced visfatin protein production in omental AT (P<0.05). Additionally, soluble leptin receptor levels rose with concentration dependency to a maximal response at leptin 10(-7) M (P<0.01). The use of a leptin antagonist negated the induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin-induced visfatin production was significantly decreased in the presence of MAPK and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin eceptor gene was knocked down using small interfering RNA, eptin-induced visfatin expression was significantly decreased. Thus, leptin increases visfatin production in AT in vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase signaling. The pleiotropic effects of leptin may be partially mediated by visfatin.

Spin transition of 1D, 2D and 3D iron(II) complex polymers - the tug-of-war between elastic interaction and a shock-absorber effect

The structures of linear chain Fe(II) spin-crossover compounds of α,β- and α,ω-bis (tetrazol-1-yl)alkane type ligands are described in relation to their magnetic properties. The first threefold interlocked 3-D catenane Fe(II) spin-transition system, [μ-tris(1,4-bis(tetrazol-1-yl)butane-N1,N1′) iron(II)] bis(perchlorate), will be discussed. An analysis is made among the structures and the cooperativity of the spin-crossover behaviour of polynuclear Fe(II) spin-transition materials.

An ex ante evaluation framework for the regional benefits of publicly supported R&D projects

This paper draws on the knowledge-base implicit in ex post evaluations of publicly funded R&D and other related conceptual and empirical studies to suggest a framework for the ex ante evaluation of the regional benefits from R&D projects. The framework developed comprises two main elements: an inventory of the global private and social benefits which might result from any R&D project; and, an assessment of the share of these global benefits which might accrue to a host region, taking into account the characteristics of the R&D project and the region's innovation system. The inventory of global benefits separately identifies private and social benefits and distinguishes between increments to public and private knowledge stocks, benefits to R&D productivity and benefits from commercialisation. Potential market and 'pure' knowledge spillovers are also considered separately. The paper concludes with the application of the framework to two illustrative case studies. © 2003 Elsevier B.V. All rights reserved.

Ethnic conflict and war crimes in the Balkans:the narratives of denial in post-conflict Serbia

In the years following the fall of Slobodan Milo evic, Serbian social, cultural and political responses to the wars of the 1990s have fallen under intense international scrutiny. But is this scrutiny justfied, and how can these responses be better understood? Jelena Obradovic engages with ideas about post-conflict societies, memory, cultural trauma, and national myths of victimhood and justified war to shed light upon Serbian denial and justification of war crimes - for example, Serbia's reluctant cooperation with the International Criminal Tribunal for the former Yugoslavia (ICTY). Rather than treating denial as a failure to come to terms with the past or as resurgent nationalism, Obradovic argues that the justification of atrocities are often the result of a societal need to understand and incorporate violent events within culturally acceptable boundaries.

The French Confederation Generale du Travail and the International Secretariat of National Trade Union Centres (1900-1914):French syndicalist attitudes towards internationalism and the International Labour Movement

This thesis examines relations between the French Confederation Generale du Travail (CGT) and the labour movements of other countries in the years leading up to the First World War. The aim of the study is to examine the CGT's policy of internationalism in practice, both in relations with other labour movements and in its membership of the International Secretariat of National Trade Union Centres (between 1900 and 1914). In particular, the relationship between the French and German labour movements is explored in the light of the events of August 1914. This study shows that the relationship was a reflection of the respective positions of the French and German labour movements in the international movement. It also subjects to close scrutiny the assumption, widely made before 1914, that workers had more in common with each other than with the ruling classes of their own country, by analysing the extent of, and the reasons for internationalism and international cooperation in the labour movement. As a study of the International Secretariat of National Trade Union Centres, an organisation about which very little has previously been written, this thesis complements existing work on the international labour movement prior to 1914. It also provides new insights into the French CGT by concentrating on the fundamental areas of internationalism and opposition to war, and offers fresh contributions to the continuing debate on the international labour movement and its response to the outbreak of war.

The formulation of artificial reference standards for use within the ELISPOT assay

Whether to assess the functionality of equipment or as a determinate for the accuracy of assays, reference standards are essential for the purposes of standardisation and validation. The ELISPOT assay, developed over thirty years ago, has emerged as a leading immunological assay in the development of novel vaccines for the assessment of efficacy. However, with its widespread use, there is a growing demand for a greater level of standardisation across different laboratories. One of the major difficulties in achieving this goal has been the lack of definitive reference standards. This is partly due to the ex vivo nature of the assay, which relies on cells being placed directly into the wells. Thus, the aim of this thesis was to produce an artificial reference standard using liposomes, for use within the assay. Liposomes are spherical bilayer vesicles with an enclosed aqueous compartment and therefore are models for biological membranes. Initial work examined pre-design considerations in order to produce an optimal formulation that would closely mimic the action of the cells ordinarily placed on the assay. Recognition of the structural differences between liposomes and cells led to the formulation of liposomes with increased density. This was achieved by using a synthesised cholesterol analogue. By incorporating this cholesterol analogue in liposomes, increased sedimentation rates were observed within the first few hours. The optimal liposome formulation from these studies was composed of 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and brominated cholesterol (Brchol) at a 16:4:12 µMol ratio, based on a significantly higher (p<0.01) sedimentation (as determined by a percentage transmission of 59 ± 5.9 % compared to the control formulation at 29 ± 12 % after four hours). By considering a range of liposome formulations ‘proof of principle’ for using liposomes as ELISPOT reference standards was shown; recombinant IFN? cytokine was successfully entrapped within vesicles of different lipid compositions, which were able to promote spot formation within the ELISPOT assay. Using optimised liposome formulations composed of phosphatidylcholine with or without cholesterol (16 µMol total lipid) further development was undertaken to produce an optimised, scalable protocol for the production of liposomes as reference standards. A linear increase in spot number by the manipulation of cytokine concentration and/or lipid concentrations was not possible, potentially due to the saturation that occurred within the base of wells. Investigations into storage of the formulations demonstrated the feasibility of freezing and lyophilisation with disaccharide cryoprotectants, but also highlighted the need for further protocol optimisation to achieve a robust reference standard upon storage. Finally, the transfer of small-scale production to a medium lab-scale batch (40 mL) demonstrated this was feasible within the laboratory using the optimised protocol.

Interned in Scotland. The Stobs Camp during the First World War

After the outbreak of war, civilians of Central Power nationality were declared ‘enemy aliens’ throughout the British Empire. Scotland serves as a representative case history to analyse patterns of public Germanophobia, ethnic minority displacement, internment, and repatriation. The Stobs camp in the Scottish Borders region was one of the biggest camps in the Empire. Internees were affected by the depressive ‘barbed wire disease’ and organised a plethora of activities. Those who were repatriated faced destitution in Germany. Neither in Britain nor in Germany have they been included in remembrance cultures. Within wider debates about the totalisation of warfare during World War I, the article takes on a global perspective to argue in favour of a stronger emphasis on civilian suffering.

‘Enemy aliens’ in wartime:civilian internment in South Africa during World War I

This article explores the previously neglected history of civilian internment in South Africa during World War I. German, Austro-Hungarian and Turkish nationals were classified as ‘enemy aliens’. They included mostly male immigrants, but also several hundred women and children deported from Sub-Saharan colonial contact zones. The main camp was Fort Napier in Pietermaritzburg, holding around 2,500. Based on sources in South African, German and British archives, this multi-perspectival enquiry highlights the salience of the South African case and integrates it into wider theoretical questions and arguments. The policy of civilian internment was rolled out comprehensively throughout the British Empire. Not least lessons learnt from the South African War (1900-1902), when Britain had been widely criticised for harsh conditions in its camps, led to relatively humane prisoner treatment. Another mitigating factor were the pro-German sympathies of the Afrikaner population. Nevertheless, suffering occurred through isolation and deportation. Remembering the First World War mainly as a ‘’soldiers’ war’ on the Western Front generates too narrow a picture. Widening the lens on civilians of both sexes in overseas territories supports notions of war totalisation.