The evolution, distribution and diversity of endogenous circoviral elements in vertebrate genomes

Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe are a useful source of information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe

Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Background: Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods: A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results: tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions: Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.GLM is supported by the National Health & Medical Research Council of Australia ID 571090

Laurent Bove e a imaginação

Este Trabalho pretende investigar como se apresenta a questão da imaginação na leitura espinosista de Laurent Bove. Esta investigação terá como base, exclusivamente, seu primeiro livro publicado no Brasil em 2010: “Espinosa e a psicologia Social: Ensaios de ontologia política e antropogênese”[1] a fim de tecer breves apontamentos sobre os papéis que a imaginação ocupa nas teorizações do filósofo francês.[1] BOVE, Laurent. Espinosa e a psicologia Social: Ensaios de ontologia política e antropogênese. Belo Horizonte: Autêntica, 2010

ANARQUISMO E VIOLÊNCIA: DEPURANDO A QUESTÃO

Este texto pretende investigar de maneira filosófica a questão da violência e seu lugar na luta entre os governantes – forças políticas e econômicas representadas pelo Estado e seu sistema Jurídico – e governados – mais especificamente as táticas de luta anarquista. Propõe-se apresentar as lógicas da violência e sua ótica nessas diferentes instâncias e seus diferentes pressupostos quando estão postas em conflito. Para isso, será realizado um diálogo entre expoentes do anarquismo clássico (Mikhail Bakunin e Piotr Kropotkin) e do contemporâneo Lorenzo Kom’boa Ervin com pensadores considerados marxistas heterodoxos que trataram deste tema (Georges Sorel e Walter Benjamin), a fim de tecer conexões insuspeitadas que auxiliem para o aprofundamento da questão

The exported protein PbCP1 localises to cleft-like structures in the rodent malaria parasite Plasmodium berghei

Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. In this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite P. berghei and provide further proof of the conserved nature of host cell remodeling in Plasmodium spp. Based on the presence of an export motif (R/KxLxE/Q/D) termed PEXEL (Plasmodium export element), we have generated transgenic P. berghei parasite lines expressing GFP chimera of putatively exported proteins and analysed one of the newly identified exported proteins in detail. This essential protein, termed PbCP1 (P. berghei Cleft-like Protein 1), harbours an atypical PEXEL motif (RxLxY) and is further characterised by two predicted transmembrane domains (2TMD) in the C-terminal end of the protein. We have functionally validated the unusual PEXEL motif in PbCP1 and analysed the role of the 2TMD region, which is required to recruit PbCP1 to discrete membranous structures in the red blood cell cytosol that have a convoluted, vesico-tubular morphology by electron microscopy. Importantly, this study reveals that rodent malaria species also induce modifications to their host red blood cell

SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling

BACKGROUND: The goal of this study was to evaluate changes in gene expression in SW-620 cells in response to SN-38 in order to further elucidate the mechanisms by which SN-38 causes apoptosis and cell cycle arrest. METHODS: We used a quantitative gene expression microarray assay to identify the genes regulated by SN-38 treatment in colon cancer cells and confirmed our results with RT-PCR. By gene expression profiling, we first screened a proprietary list of about 22,000 genes. RESULTS: Treatment with SN-38 cells resulted in two-fold or greater alteration in the level of expression of 192 genes compared to control treatment. Most of the affected genes were not known to be responsive to SN-38 prior to this study. SN-38 treatment of these cells was found to affect the expression of various genes involved in DNA replication, transcription, signal transduction, growth factors, cell cycle regulation, and apoptosis, as well as other genes with unknown function. Changes in expression of 14 genes were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). CONCLUSION: This study leads to an increased understanding of the biochemical pathways involved in SN-38-induced apoptosis and possibly to the identification of new therapeutic targets

Sex-Biased Expression of MicroRNAs in Schistosoma mansoni

Schistosomiasis is an important neglected tropical disease caused by digenean helminth parasites of the genus Schistosoma. Schistosomes are unusual in that they are dioecious and the adult worms live in the blood system. MicroRNAs play crucial roles during gene regulation and are likely to be important in sex differentiation in dioecious species. Here we characterize 112 microRNAs from adult Schistosoma mansoni individuals, including 84 novel microRNA families, and investigate the expression pattern in different sexes. By deep sequencing, we measured the relative expression levels of conserved and newly identified microRNAs between male and female samples. We observed that 13 microRNAs exhibited sex-biased expression, 10 of which are more abundant in females than in males. Sex chromosomes showed a paucity of female-biased genes, as predicted by theoretical evolutionary models. We propose that the recent emergence of separate sexes in Schistosoma had an effect on the chromosomal distribution and evolution of microRNAs, and that microRNAs are likely to participate in the sex differentiation/maintenance process

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia