Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors Pseudospumigins by the Brazilian Benthic Nostoc sp CENA543

Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolandia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena. We also characterized pseudospumigins A-F, which are a novel family of linear tetrapeptides. Pseudospumigins are structurally related to linear tetrapeptide spumigins and aeruginosins both present in N. spumigena but differ in respect to their diagnostic amino acid, which is Ile/Leu/Val in pseudospumigins, Pro/mPro in spumigins, and Choi in aeruginosins. The pseudospumigin gene cluster is more similar to the spumigin biosynthetic gene cluster than the aeruginosin gene cluster. Pseudospumigin A inhibited trypsin (IC50 4.5 mu M after 1 h) in a similar manner as spumigin E from N. spumigena but was almost two orders of magnitude less potent. This study identifies another location and environment where the hepatotoxic nodularin has the potential to cause the death of eukaryotic organisms.Peer reviewe

Sport, War and Democracy in Classical Athens

This article concerns the paradox of athletics in classical Athens. Democracy may have opened up politics to every class of Athenian but it had little impact on sporting participation. The city’s athletes continued to drawn predominantly from the upper class. It comes as a surprise then that lower-class Athenians actually esteemed athletes above every other group in the public eye, honoured them very generously when they won, and directed a great deal of public and private money to sporting competitions and facilities. In addition athletics escaped the otherwise persistent criticism of upper-class activities in the popular culture of the democracy. The research of social scientists on sport and aggression suggests this paradox may have been due to the cultural overlap between athletics and war under the Athenian democracy. The article concludes that the practical and ideological democratization of war by classical Athens legitimized and supported upper-class sport

Assessing the sociology of sport: On globalization and the diffusion of sport

This paper was accepted for publication in the journal, International Review for the Sociology of Sport. The definitive version is available at: http://dx.doi.org/10.1177/1012690214547374.On the 50th anniversary of the ISSA and IRSS, a key foundational scholar on the increasing globalization of sport, Joseph Maguire, considers larger questions about the diffusion of sport in light of the tendencies of globalization. The essay considers the ‘current state of play’ about the ‘known dimensions’ of the globalization of sport, commenting on how British and European influences on standards and conventions gave way to North American (in particular, US) influences on increasing professional norms and the embedding of commodification. In considering challenges to the West and to Western scholars of sport and globalization, the Soviet bloc’s sustained challenges to Western dominance are noted, as are non-Western successes in select sports and recent Chinese success accelerated by the 2008 Beijing Olympic Games. The essay closes by considering five priorities in future directions for research on sport and globalization, all stemming from inquiry about continuities and changes in the global sport power elite and the ways in which this is both understood and resisted

Discovery of varlaxins, new aeruginosin-type inhibitors of human trypsins

Low-molecular weight natural products display vast structural diversity and have played a key role in the development of novel therapeutics. Here we report the discovery of novel members of the aeruginosin family of natural products, which we named varlaxins. The chemical structures of varlaxins 1046A and 1022A were determined using a combination of mass spectrometry, analysis of one- and two-dimensional NMR spectra, and HPLC analysis of Marfey’s derivatives. These analyses revealed that varlaxins 1046A and 1022A are composed of the following moieties: 2-O-methylglyceric acid 3-O-sulfate, isoleucine, 2-carboxy-6-hydroxyoctahydroindole (Choi), and a terminal arginine derivative. Varlaxins 1046A and 1022A differ in the cyclization of this arginine moiety. Interestingly, an unusual α-D-glucopyranose moiety derivatized with two 4-hydroxyphenylacetic acid residues was bound to Choi, a structure not previously reported for other members of the aeruginosin family. We sequenced the complete genome of Nostoc sp. UHCC 0870andidentified the putative 36 kb varlaxin biosynthetic gene cluster. Bioinformatics analysis confirmed that varlaxins belong to the aeruginosin family of natural products. Varlaxins 1046A and 1022A strongly inhibited the three human trypsin isoenzymes with IC50 of 0.62–3.6 nM and 97–230 nM, respectively, including a prometastatic trypsin-3, which is a therapeutically relevant target in several types of cancer. These results substantially broaden the genetic and chemical diversity of the aeruginosin family and provide evidence that the aeruginosin family is a source of strong inhibitors of human serine proteases.peerReviewe