Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis

This work was supported by Marie Curie Postdoctoral Fellowships to T.A.W., E. H. and S. L., a European Research Council Advanced Investigator Grant (ERC-2010-AdG-268701) to T.M.E., and a Wellcome Trust Programme Grant (number 045404) to T.M.E. and J.M.L. R.L. acknowledges generous financial support from Deutsche Forschungsgemeinschaft (SFB 593, SFB 987, GRK 1216, LI 415/5), LOEWE program of state Hessen, Max-Planck Gesellschaft, von Behring-Röntgen StiftungMicrosporidians are a diverse group of obligate intracellular parasites that have minimized their genome content and simplified their sub-cellular structures by reductive evolution. Functional studies are limited because we lack reliable genetic tools for their manipulation. Here, we demonstrate that the cristae-deficient mitochondrion (mitosome) of the microsporidian Trachipleistophora hominis is the functional site of iron-sulphur cluster (ISC) assembly, which we suggest is the essential task of this organelle. Cell fractionation, fluorescence imaging and fine-scale immunoelectron microscopy demonstrate that mitosomes contain a complete pathway for [2Fe-2S] cluster biosynthesis that we biochemically reconstituted using purified recombinant mitosomal ISC proteins. Reconstitution proceeded as rapidly and efficiently as observed for yeast or fungal mitochondrial ISC components. Core components of the T. hominis cytosolic iron-sulphur protein assembly (CIA) pathway were also identified including the essential Cfd1-Nbp35 scaffold complex that assembles a [4Fe-4S] cluster as shown by spectroscopic methods in vitro. Phylogenetic analyses reveal that both the ISC and CIA biosynthetic pathways are predominantly bacterial, but their cytosolic and nuclear target Fe/S proteins are mainly archaeal. This mixed evolutionary history of the Fe/S-related proteins and pathways, and their strong conservation among highly reduced parasites, provides additional compelling evidence for the ancient chimeric ancestry of eukaryotes.Publisher PDFPeer reviewe

Wellbeing and chronic lung disease incidence: The Survey of Health, Ageing and Retirement in Europe

Judith A. Okely and Catharine R. Gale are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged

The genome of the obligate intracellular parasite Trachipleistophora hominis : new insights into microsporidian genome dynamics and reductive evolution

The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but not all, lineages.Publisher PDFPeer reviewe

Work organization and the health of bank employees Organización del trabajo y salud de empleados del banco Organização do trabalho e saúde de trabalhadores bancários

The Brazilian banking sector has undergone an intense restructuring process and taken a leading position in the incorporation of new technologies and organizational innovations. Computerization in the industry, in association with forms of work organization, has resulted in changes that reflect on the workers' health. Based on the theoretical and methodological frameworks of historical and dialectical materialism, this qualitative study investigates the work conditions of bank employees in order to identify the extent to which changes in work organization interfere with these workers' health. Data were collected through interviews held with 11 bank employees. In addition to physical sickening due to occupational diseases directly related to work intensification, the results also show an increased incidence of mental suffering and a feeling of loss of professional identity. Work-related frustration, instability and concerns related to psychological pressure resulting from the need to achieve goals predominated in the reports.<br>La Banca Brasileña pasó por un intenso proceso de reestructuración y ha ocupado posiciones de liderazgo en la incorporación de nuevas tecnologías e innovaciones organizacionales. La informatización de la industria, junto con nuevas maneras de organización del trabajo, dio lugar a cambios que reflejaron en la salud de los trabajadores. Con base en el marco teórico y metodológico del materialismo histórico y dialéctico, este estudio cualitativo tuvo como objetivo investigar las condiciones laborales de los empleados del banco para identificar el grado en que los cambios en la organización del trabajo influyeron en la salud de los trabajadores. Los datos fueron recolectados a través de entrevistas con once empleados del banco. Los resultados mostraron, además de las enfermedades físicas profesionales directamente relacionadas con la intensificación del trabajo, aumento de la incidencia de sufrimiento mental y la sensación de pérdida de identidad profesional. Predominaron en las entrevistas sentimientos de frustración e inseguridad sobre el trabajo y la preocupación por la presión psicológica de la necesidad de logro de los objetivos.<br>O setor bancário brasileiro passou por intenso processo de reestruturação e ocupou posição de liderança na incorporação de novas tecnologias e inovações organizacionais. A informatização do setor, aliada às novas formas de organizar o trabalho, resultou em mudanças que refletiram na saúde dos trabalhadores. Fundamentado no referencial teórico metodológico do materialismo histórico-dialético, este estudo, de caráter qualitativo, teve por objetivo investigar as condições de trabalho de bancários, para identificar em que medida as mudanças na organização do trabalho interferiram na saúde daqueles trabalhadores. Os dados foram coletados através de entrevistas com onze bancários. Os resultados revelaram, além de adoecimentos de ordem física por doenças ocupacionais, diretamente relacionadas à intensificação do trabalho, o aumento da incidência de sofrimento mental e sentimento de perda de identidade profissional. Predominaram, nos depoimentos, sentimentos de frustração e insegurança em relação ao trabalho e preocupação com a pressão psicológica, derivada da necessidade de cumprimento de metas

Treinamento de natação na intensidade do limiar anaeróbio melhora a aptidão funcional de ratos idosos Swimming training at anaerobic threshold intensity improves the functional fitness of older rats

Os efeitos do treinamento aeróbio em intensidade relativa ao limiar de lactato (LL) foram analisados em 15 ratos idosos (~448 dias de vida). Os grupos de animais treinados (n=9) e controle (n=6) foram submetidos a um teste antes e após quatro semanas de treinamento. O teste incremental consistiu de uma carga inicial de 1% do peso corporal e incrementos de 1% a cada três minutos, com mensurações de lactato sanguíneo para identificação do LL por inspeção visual do ponto de inflexão da curva. O programa de treinamento consistiu de 30 minutos de natação/dia, cinco dias/semana, com sobrecarga de 5% do peso corporal (PC), ou controle sem exercício. Foi observado aumento significativo na intensidade do LL após o treinamento (pré = 4,5 ± 1,1 vs. Pós = 5.4 ± 0.9% PC). A carga máxima atingida ao final do teste incremental aumentou significativamente de 39,7 ± 7,5g no pré para 48,4 ± 10,5g no pós treinamento, sem mudanças para o grupo controle (44,7 ± 8 vs. 45,3 ± 9,3g). O peso corporal do grupo treinado não apresentou diferença como resultado de quatro semanas de natação em intensidade correspondente ao LL (641,0 ±62,0 para 636,0 ± 72.7g; p>0.05). Por outro lado, o grupo não treinado aumentou significativamente o PC de 614,0 ± 8,0 para 643,0 ± 74,1g. A carga máxima atingida expressa tanto em valores absolutos como relativos (%PC) aumentou significativamente após o treinamento. Conclui-se que quatro semanas de treinamento de natação em intensidade correspondente ao limiar de lactato resultou em uma melhora da aptidão aeróbia e na manutenção do peso corporal em ratos idosos.<br>The effects of aerobic training at the lactate threshold (LT) intensity were analyzed in fifteen older rats (~448 days old). Both the trained (n = 9) and control (n = 6) groups were submitted to an incremental exercise test before and after four weeks of training. The incremental exercise test consisted of an initial load of 1% BM and 1% increments at each 3-min with blood lactate measurements. The LT was determined by visual inspection of the blood lactate breakpoint. The training program comprised of 30-min swimming/day, 5 days/week, loaded with 5% body mass (BM), or control without exercise. Significant increase on the LT intensity after training (pre = 4.5 ± 1.1 vs. post = 5.4 ± 0.9% BM). The maximal workload reached at the end of incremental test increased significantly from 39.7 ± 7.5 g on pre to 48.4 ± 10.5 g at post training, with no changes for the control group (44.7 ± 8 vs. 45.3 ± 9.3 g). The body mass of the trained group did not change as a result of 4 weeks of swimming at LT intensity (641.0 ± 62.0 to 636.0 ± 72.7 g; p > 0.05). On the other hand, the untrained group increased significantly the BM from 614.0 ± 80.0 to 643.0 ± 72.7 g. The maximal workload, as expressed both in relation to absolute and relative values (i.e. %BM) increased significantly only as a result of training. It was concluded that four weeks of swimming training at LT intensity resulted in aerobic fitness improvement and body mass maintenance of older rats