Trypanosoma rangeli is phylogenetically closer to Old World trypanosomes than to Trypanosoma cruzi.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.This study was supported by grants awarded to MMGT and EPC from CNPq (National Council for Scientific and Technological Development) PROAFRICA, PROSUL and UNIVERSAL programs, CAPES (Coordination for the Improvement of Higher Education Personnel) PNIPB, PNPD and PROTAX programs, and FAPESP (São Paulo Research Foundation; process 2016/07487-0). Genome sequencing was supported by the Assembling the Tree of Life (ATOL) Project of the National Science Foundation, USA (NSF DEB-0830056), and TCC-USP (Trypanosomatid Culture Collection of the University of São Paulo) projects. OEA received PhD fellowships from CNPq (PROTAX) and COLCIENCIAS (Administrative Department of Science, Technology and Innovation, Colombia); PAO is a postdoctoral fellow of CAPES (PNPD); LL and AGCM are supported by a postdoctoral fellowship from CAPES (PROTAX)

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Phylogenetic Analysis of Bolivian Bat Trypanosomes of the Subgenus Schizotrypanum Based on Cytochrome b Sequence and Minicircle Analyses

The aim of this study was to establish the phylogenetic relationships of trypanosomes present in blood samples of Bolivian Carollia bats. Eighteen cloned stocks were isolated from 115 bats belonging to Carollia perspicillata (Phyllostomidae) from three Amazonian areas of the Chapare Province of Bolivia and studied by xenodiagnosis using the vectors Rhodnius robustus and Triatoma infestans (Trypanosoma cruzi marenkellei) or haemoculture (Trypanosoma dionisii). The PCR DNA amplified was analyzed by nucleotide sequences of maxicircles encoding cytochrome b and by means of the molecular size of hyper variable regions of minicircles. Ten samples were classified as Trypanosoma cruzi marinkellei and 8 samples as Trypanosoma dionisii. The two species have a different molecular size profile with respect to the amplified regions of minicircles and also with respect to Trypanosoma cruzi and Trypanosoma rangeli used for comparative purpose. We conclude the presence of two species of bat trypanosomes in these samples, which can clearly be identified by the methods used in this study. The presence of these trypanosomes in Amazonian bats is discussed

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Predator Mimicry: Metalmark Moths Mimic Their Jumping Spider Predators

Cases of mimicry provide many of the nature's most convincing examples of natural selection. Here we report evidence for a case of predator mimicry in which metalmark moths in the genus Brenthia mimic jumping spiders, one of their predators. In controlled trials, Brenthia had higher survival rates than other similarly sized moths in the presence of jumping spiders and jumping spiders responded to Brenthia with territorial displays, indicating that Brenthia were sometimes mistaken for jumping spiders, and not recognized as prey. Our experimental results and a review of wing patterns of other insects indicate that jumping spider mimicry is more widespread than heretofore appreciated, and that jumping spiders are probably an important selective pressure shaping the evolution of diurnal insects that perch on vegetation

Structural equation and log-linear modeling: a comparison of methods in the analysis of a study on caregivers' health

BACKGROUND: In this paper we compare the results in an analysis of determinants of caregivers' health derived from two approaches, a structural equation model and a log-linear model, using the same data set. METHODS: The data were collected from a cross-sectional population-based sample of 468 families in Ontario, Canada who had a child with cerebral palsy (CP). The self-completed questionnaires and the home-based interviews used in this study included scales reflecting socio-economic status, child and caregiver characteristics, and the physical and psychological well-being of the caregivers. Both analytic models were used to evaluate the relationships between child behaviour, caregiving demands, coping factors, and the well-being of primary caregivers of children with CP. RESULTS: The results were compared, together with an assessment of the positive and negative aspects of each approach, including their practical and conceptual implications. CONCLUSION: No important differences were found in the substantive conclusions of the two analyses. The broad confirmation of the Structural Equation Modeling (SEM) results by the Log-linear Modeling (LLM) provided some reassurance that the SEM had been adequately specified, and that it broadly fitted the data

Inactivation of respiratory syncytial virus by zinc finger reactive compounds

<p>Abstract</p> <p>Background</p> <p>Infectivity of retroviruses such as HIV-1 and MuLV can be abrogated by compounds targeting zinc finger motif in viral nucleocapsid protein (NC), involved in controlling the processivity of reverse transcription and virus infectivity. Although a member of a different viral family (<it>Pneumoviridae</it>), respiratory syncytial virus (RSV) contains a zinc finger protein M2-1 also involved in control of viral polymerase processivity. Given the functional similarity between the two proteins, it was possible that zinc finger-reactive compounds inactivating retroviruses would have a similar effect against RSV by targeting RSV M2-1 protein. Moreover, inactivation of RSV through modification of an internal protein could yield a safer whole virus vaccine than that produced by RSV inactivation with formalin which modifies surface proteins.</p> <p>Results</p> <p>Three compounds were evaluated for their ability to reduce RSV infectivity: 2,2'-dithiodipyridine (AT-2), tetraethylthiuram disulfide and tetramethylthiuram disulfide. All three were capable of inactivating RSV, with AT-2 being the most potent. The mechanism of action of AT-2 was analyzed and it was found that AT-2 treatment indeed results in the modification of RSV M2-1. Altered intramolecular disulfide bond formation in M2-1 protein of AT-2-treated RSV virions might have been responsible for abrogation of RSV infectivity. AT-2-inactivated RSV was found to be moderately immunogenic in the cotton rats <it>S.hispidus </it>and did not cause a vaccine-enhancement seen in animals vaccinated with formalin-inactivated RSV. Increasing immunogenicity of AT-2-inactivated RSV by adjuvant (Ribi), however, led to vaccine-enhanced disease.</p> <p>Conclusions</p> <p>This work presents evidence that compounds that inactivate retroviruses by targeting the zinc finger motif in their nucleocapsid proteins are also effective against RSV. AT-2-inactivated RSV vaccine is not strongly immunogenic in the absence of adjuvants. In the adjuvanted form, however, vaccine induces immunopathologic response. The mere preservation of surface antigens of RSV, therefore may not be sufficient to produce a highly-efficacious inactivated virus vaccine that does not lead to an atypical disease.</p

Evidence and morality in harm-reduction debates: can we use value-neutral arguments to achieve value-driven goals?

It is common to argue that politicians make selective use of evidence to tacitly reinforce their moral positions, but all stakeholders combine facts and values to produce and use research for policy. The drug policy debate has largely been framed in terms of an opposition between evidence and politics. Focusing on harm reduction provides useful ground to discuss a further opposition proposed by evidence advocates, that between evidence and morality. Can evidence sway individuals from their existing moral positions, so as to “neutralise” morality? And if not, then should evidence advocates change the way in which they frame their arguments? To address these questions, analysis of N=27 interviews with stakeholders involved in drug policy and harm reduction research, advocacy, lobbying, implementation and decision-making in England, UK and New South Wales, Australia, was conducted. Participants’ accounts suggest that although evidence can help focus discussions away from values and principles, exposure to evidence does not necessarily change deeply held views. Whether stakeholders decide to go with the evidence or not seems contingent on whether they embrace a view of evidence as secular faith; a view that is shaped by experience, politics, training, and role. And yet, morality, values, and emotions underpin all stakeholders’ views, motivating their commitment to drug policy and harm reduction. Evidence advocates might thus benefit from morally and emotionally engaging audiences. This paper aims to develop better tools for analysing the role of morality in decision-making, starting with moral foundations theory. Using tools from disciplines such as moral psychology is relevant to the study of the politics of evidence-based policymaking