Over the last ten years the gap year has become a popular and publicly recognized phenomenon. One of the most visible forms of this phenomenon has been the emergence of 'third world' volunteer-tourism programmes, which seek to combine the hedonism of tourism with the altruism of development work. Such programmes make the practice of international development doable, knowable and accessible to young travellers. This paper seeks to critique the construction of this public face of development, while also asking, from a pedagogical perspective, what travelling participants learn about 'the others' they encounter on, and through, such programmes.
Sixty-eight Actinoplanes isolates from freshwater sediments were compared through 89 unit characters with marker strains of the genera Actinoplanes, Ampullariella, Dactylosporangium, Micromonospora, Planobispora, Spirillospora and Streptosprangium. The data were examined using the simple matching, Jaccard and pattern coefficients and clustering was achieved using the unweighted pair group method with arithmetic averages algorithm. The numerical classification was only marginally affected by the statistics used or by test error, estimated at 5%. Most of the environmental isolates were recovered in five major clusters that were equated with taxospecies. Seven major, nine minor and 29 single-member clusters defined by the SSM coefficient at the 83% similarity (S-) level, were assigned to two aggregate groups circumscribed at the 68% S-level. The first cluster group was composed of strains belonging to the genera Actinoplanes (including Ampullariella), Dactylosporangium and Micromonospora and the second included representatives of the genera Planobispora, Planomonospora, Spirillospora and Streptosporangium. Selected Actinoplanes strains subjected to chemical analyses contained complex mixtures of straight-and branched-chain fatty acids, tetrahydrogenated menaquinones with nine isoprene units as the predominant isoprenologue, and major amounts of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol; the representative environmental isolates were also shown to contain meso-and hydroxydiaminopimelic acid; the principal wall sugars were arabinose, galactose, glucose, mannose and xylose. The chemical and numerical taxonomic data support the integrity of established species of Actinoplanes, with the exception of Actinoplanes caeruleus, and show that the five major clusters encompassing environmental isolates merit the rank of species. It is proposed that the five novel taxa be assigned to the genus Actinoplanes as Actinoplanes consettensis sp. nov., Actinoplanes derwentensis sp. nov., Actinoplanes durhamensis sp. nov., Actinoplanes humidus sp. nov., and Actinoplanes palleronii sp. nov. Similarly, the genera Actinoplanes, Dactylosporangium, Micromonospora and Pilimelia have many properties in common and it is proposed that they be classified in the family Micromonosporaceae Krassilnikov 1938; an emended description of this taxon is given. The family Streptosporangiaceae fam. nov. is proposed to accommodate organisms assigned to the genera Microbispora, Microtetraspora, Planobispora, Planomonospora and Streptosporangium.
Leaving school and dropping out of employment or further education was once an act of rebellion by cohorts of young people expressing anti-establishment sentiments. Now it has become a neoliberal market place in the UK. Over the last five years the ''gap year'' has changed from a radical activity, dominated by charities and inspired by the travel of the hippie generation, to an institutionally accepted commercial gap year industry which helps form new citizens for a global age. This transformation has seen the dramatic growth in commercial gap year companies and in the numbers of young people in the UK taking gap years. Such growth, taking place under an increasingly engaged public gaze, has led to the professionalisation of the sector and to profound changes in its underlying values. Drawing on a range of empirical sources, I examine how the transformation of the gap year through the neoliberal market place has involved the application of corporate values and rhetoric to youth travel. Becoming ''professional'' has entailed a shift from collective idealism to the infinitely more saleable values of individual career development. While professional values give legitimacy to the gap year industry, its professional gaze is also proving to be relatively myopic-it has yet to be turned on the volunteer development projects through which many companies in the industry make their names, and money.
The peptide hormone human relaxin-2 (H2-RLX) has emerged as a potential therapy for cardiovascular and fibrotic diseases, but its short in vivo half-life is an obstacle to long-term administration. The discovery of ML290 demonstrated that it is possible to identify small molecule agonists of the cognate G-protein coupled receptor for H2-RLX (relaxin family peptide receptor-1 (RXFP1)). In our efforts to generate a new medicine for liver fibrosis, we sought to identify improved small molecule functional mimetics of H2-RLX with selective, full agonist or positive allosteric modulator activity against RXFP1. First, we confirmed expression of RXFP1 in human diseased liver. We developed a robust cellular cAMP reporter assay of RXFP1 signaling in HEK293 cells transiently expressing RXFP1. A high-throughput screen did not identify further specific agonists or positive allosteric modulators of RXFP1, affirming the low druggability of this receptor. As an alternative approach, we generated novel ML290 analogues and tested their activity in the HEK293-RXFP1 cAMP assay and the human hepatic cell line LX-2. Differences in activity of compounds on cAMP activation compared with changes in expression of fibrotic markers indicate the need to better understand cell- and tissue-specific signaling mechanisms and their disease-relevant phenotypes in order to enable drug discovery.
High-throughput cell-based techniques that permit early detection of compound-induced genotoxic damage have recently become available. Methods based on induction of the GADD45a promoter are attractive because multiple intracellular mechanisms that detect genetic damage intersect at this checkpoint gene. Consequently, assays such as GreenScreen HC, which uses p53-competant human TK6 lymphoblastoid cells and a GADD45a-GFP reporter, have been developed. GreenScreen HC allows weekly testing of dozens of compounds using 96-well microplates, with high interassay consistency. BlueScreen HC is a recent advancement, coupling GADD45a to Gaussia luciferase, with several advantages over GADD45a-GFP including the potential for miniaturization. Here we describe implementation of a 384-well BlueScreen assay. For drug discovery programs carrying out iterative analogue synthesis around a chemical lead series, these assays permit assessment of compound genotoxic potential in parallel to, rather than subsequent to, determination of activity at a therapeutic target. We demonstrate comparability of BlueScreen-384 to GreenScreen HC and illustrate the use of BlueScreen-384 to explore the structure-activity relationship around a genotoxic lead molecule to identify nongenotoxic analogues. BlueScreen-384 can reduce the need for costly and time-consuming analogue testing in more traditional genotoxicity tests, such as the Ames test.
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