The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia

This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O2) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO2) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO2 was significantly improved (median pO2=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion

The Transformation of Citizenship in Complex Societies

The main purpose of this paper is to propose a theoretical framework for understanding the transformation of citizenship in complex societies. To this end, the paper is divided into six sections. The first section elucidates the main reasons for the renaissance of the concept of citizenship in the contemporary social sciences. The second section argues that a comprehensive sociological theory of citizenship needs to account for the importance of four dimensions: the content, the type, the conditions, and the arrangements of citizenship. The third section suggests that in order to understand the sociological significance of T.H. Marshall’s account of legal, political, and social rights we need to explore the particular historical contexts in which citizenship rights became ideologically and institutionally relevant. The fourth section offers some critical reflections on the main shortcomings of the Marshallian approach to citizenship. The fifth section draws an analogy between the transformation of social movements and the transformation of citizenship. The sixth section sheds light on the fact that contemporary citizenship studies are confronted with a curious paradox: the differentiation of citizenship has led to both the relativistic impoverishment and the pluralistic enrichment of contemporary accounts of ‘the social’ and ‘the political’.The paper concludes by arguing that, under conditions of late modernity, the state’s capacity to gain political legitimacy increasingly depends on its ability to confront the normative challenges posed by the ubiquity of societal complexity

Some salt with your statin, professor?

We know that clinical trials sponsored by the pharmaceutical industry are likely to exaggerate benefit and minimise harms. But do these biases extend to their sponsorship of non-human animal research? Using systematic review and meta-analysis Bero and colleagues show that, in the case of statins, things are a little more complicated. While the conclusions of industry-sponsored studies were indeed more enthusiastic than warranted by their data, the data themselves painted a picture more conservative than was seen in non-industry-sponsored studies. This behaviour is consistent with maximising the return on investment, seeking robust data before embarking on a clinical trial, and, once that investment has been made, making every effort to “prove” that the drug is safe and effective if this is at all credible. The findings suggest that there is something different about industry-sponsored non-human animal research, perhaps reflecting higher standards than is the case elsewhere. Perhaps the academic community can learn something from our colleagues in the commercial sector

Improving our understanding of the in vivo modelling of psychotic disorders: a systematic review and meta-analysis

Psychotic disorders represent a severe category of mental disorders affecting about one percent of the population. Individuals experience a loss or distortion of contact with reality alongside other symptoms, many of which are still not adequately managed using existing treatments. While animal models of these disorders could offer insights into these disorders and potential new treatments, translation of this knowledge has so far been poor in terms of informing clinical trials and practice. The aim of this project was to improve our understanding of these pre-clinical studies and identify potential weaknesses underlying translational failure. I carried out a systematic search of the literature to provide an unbiased summary of publications reporting animal models of schizophrenia and other psychotic disorders. From these publications, data were extracted to quantify aspects of the field including reported quality of studies, study characteristics and behavioural outcome data. The latter of these data were then used to calculate estimates of efficacy using random-effects meta-analysis. Having identified 3847 publications of relevance, including 852 different methods used to induce the model, over 359 different outcomes tested in them and almost 946 different treatments reported to be administered. I show that a large proportion of studies use simple pharmacological interventions to induce their models of these disorders, despite the availability of models using other interventions that are arguably of higher translational relevance. I also show that the reported quality of these studies is low, and only 22% of studies report taking measures to reduce the risk of biases such as randomisation and blinding, which has been shown to affect the reliability of results drawn. Through this work it becomes apparent that the literature is incredibly vast for studies looking at animal models of psychotic disorders and that some of the relevant work potentially overlaps with studies describing other conditions. This means that drawing reliable conclusions from these data is affected by what is made available in the literature, how it is reported and identified in a search and the time that it takes to reach these conclusions. I introduce the idea of using computer-assisted tools to overcome one of these problems in the long term. Translation of results from studies looking at animals modelling uniquely-human psychotic disorders to clinical successes might be improved by better reporting of studies including publishing of all work carried out, labelling of studies more uniformly so that it is identifiable, better reporting of study design including improving on reporting of measures taken to reduce the risk of bias and focusing on models with greater validity to the human condition

Team Learning: the Missing Construct from a Cross-Cultural Examination of Higher Education?

Team learning should be an important construct in organizational management research because team learning can enhance organizational learning and overall performance. However, there is limited understanding of how team learning works in different cultural contexts. Using an international comparative research approach, we developed a framework of antecedents and outcomes in the higher education context and tested it with samples from the UK and Vietnam. The results show that a common framework is applicable in the two different contexts, subject to slight modifications. However, this study does not find that team learning (measured via the proxy of “attitude towards team learning”) exhibits any statistically significant relationship as a predictor of the proposed outcomes. Other findings from this study on educational contexts are important not only to scholars in this field, but also for practicing managers, particularly those who study and operate in the extensive global market

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis

Management control systems in innovation companies: A literature based framework

Past research has traditionally argued that management control systems (MCSs) may present a hindrance to the creativity of innovation companies. This theoretical paper surveys the literature to focus an investigation on the MCSs of innovation companies. Within the object of control paradigm the paper develops and presents a theoretical model of the impact of eleven external, organisational and innovation related contingency factors on the MCSs in companies that engage in innovation activities. We also suggest measures for further empirical research. By formulating hypotheses on 43 potential interactions the model predicts contradictory influences on two direct control categories, results and action control, but stresses the importance of two indirect categories, personnel and cultural control. More specifically, the high levels of technological complexity and innovation capability in this type of company are expected to be negatively associated with the application of results and action control, whereas personnel and cultural seem to be more appropriate. Furthermore, important sources of finance, venture capital and public funding, are both hypothesised to be positively associated with the application of results, action and personnel control; whereas only public funding is predicted to be positively related to the application of cultural control. The principal contribution of this paper lies in synthesising the literature to provide a model of the impact of a unique set of eleven contingency factors for innovation companies on a broad scope of controls. In addition, the contingency model, if empirically validated, would add value by inferring the particular forms of management control which would be beneficial in innovative company settings. © 2014 Springer-Verlag Berlin Heidelberg

The comparative biology of New Zealand oystercatchers

Oystercatchers comprise a distinctive group of mollusc-eating shorebirds. They form an extremely uniform monogeneric family which has not undergone any major adaptive radiations into a diversity of ecological niches, but rather has dispersed from original centres of distribution to occupy identical niches in new geographical localities. The uniformity of structure and habit displayed within the group has been attributed by Larson (1957) to a high ecobiotic specialisation with centripetal selection involved. Throughout their range, oystercatchers exploit identical ecological niches which require specialised habits for successful utilisation. The specialised feeding habits of oystercatchers are well documented (Murphy, 1925; Dewar, 1940; Larson, 1957; Tinbergen and Norton-Griffiths, 1964; Dare, 1966), and a natural consequence of this specialisation is that it is restrictive to adaptive radiation