The parasite Trichomonas vaginalis expresses thousands of pseudogenes and long non-coding RNAs independently from functional neighbouring genes

BACKGROUND: The human pathogen Trichomonas vaginalis is a parabasalian flagellate that is estimated to infect 3% of the world’s population annually. With a 160 megabase genome and up to 60,000 genes residing in six chromosomes, the parasite has the largest genome among sequenced protists. Although it is thought that the genome size and unusual large coding capacity is owed to genome duplication events, the exact reason and its consequences are less well studied. RESULTS: Among transcriptome data we found thousands of instances, in which reads mapped onto genomic loci not annotated as genes, some reaching up to several kilobases in length. At first sight these appear to represent long non-coding RNAs (lncRNAs), however, about half of these lncRNAs have significant sequence similarities to genomic loci annotated as protein-coding genes. This provides evidence for the transcription of hundreds of pseudogenes in the parasite. Conventional lncRNAs and pseudogenes are expressed in Trichomonas through their own transcription start sites and independently from flanking genes in Trichomonas. Expression of several representative lncRNAs was verified through reverse-transcriptase PCR in different T. vaginalis strains and case studies exclude the use of alternative start codons or stop codon suppression for the genes analysed. CONCLUSION: Our results demonstrate that T. vaginalis expresses thousands of intergenic loci, including numerous transcribed pseudogenes. In contrast to yeast these are expressed independently from neighbouring genes. Our results furthermore illustrate the effect genome duplication events can have on the transcriptome of a protist. The parasite’s genome is in a steady state of changing and we hypothesize that the numerous lncRNAs could offer a large pool for potential innovation from which novel proteins or regulatory RNA units could evolve. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-906) contains supplementary material, which is available to authorized users

Enhancing integrated indoor/outdoor mobility in a smart campus

A Smart City relies on six key factors: Smart Governance, Smart People, Smart Economy, Smart Environment, Smart Living and Smart Mobility. This paper focuses on Smart Mobility by improving one of its key components: positioning. We developed and deployed a novel indoor positioning system (IPS) that is combined with an outdoor positioning system to support seamless indoor and outdoor navigation and wayfinding. The positioning system is implemented as a service in our broader cartography-based smart university platform, called SmartUJI, which centralizes access to a diverse collection of campus information and provides basic and complex services for the Universitat Jaume I (Spain), which serves as surrogate of a small city. Using our IPS and based on the SmartUJI services, we developed, deployed and evaluated two end-user mobile applications: the SmartUJI APP that allows users to obtain map-based information about the different facilities of the campus, and the SmartUJI AR that allows users to interact with the campus through an augmented reality interface. Students, university staff and visitors who tested the applications reported their usefulness in locating university facilities and generally improving spatial orientation

A sea slug's guide to plastid symbiosis

Some 140 years ago sea slugs that contained chlorophyll-pigmented granules similar to those of plants were described. While we now understand that these “green granules” are plastids the slugs sequester from siphonaceous algae upon which they feed, surprisingly little is really known about the molecular details that underlie this one of a kind animal-plastid symbiosis. Kleptoplasts are stored in the cytosol of epithelial cells that form the slug’s digestive tubules, and one would guess that the stolen organelles are acquired for their ability to fix carbon, but studies have never really been able to prove that. We also do not know how the organelles are distinguished from the remaining food particles the slugs incorporate with their meal and that include algal mitochondria and nuclei. We know that the ability to store kleptoplasts long-term has evolved only a few times independently among hundreds of sacoglossan species, but we have no idea on what basis. Here we take a closer look at the history of sacoglossan research and discuss recent developments. We argue that, in order to understand what makes this symbiosis work, we will need to focus on the animal’s physiology just as much as we need to commence a detailed analysis of the plastids’ photobiology. Understanding kleptoplasty in sacoglossan slugs requires an unbiased multidisciplinary approach

Genetic autonomy and low singlet oxygen yield support kleptoplast functionality in photosynthetic sea slugs

The kleptoplastic sea slug Elysia chlorotica consumes Vaucheria litorea, stealing its plastids, which then photosynthesize inside the animal cells for months. We investigated the properties of V. litorea plastids to understand how they withstand the rigors of photosynthesis in isolation. Transcription of specific genes in laboratory-isolated V. litorea plastids was monitored for 7 days. The involvement of plastid-encoded FtsH, a key plastid maintenance protease, in recovery from photoinhibition in V. litorea was estimated in cycloheximide-treated cells. In vitro comparison of V. litorea and spinach thylakoids was applied to investigate reactive oxygen species formation in V. litorea. In comparison to other tested genes, the transcripts of ftsH and translation elongation factor EF-Tu (tufA) decreased slowly in isolated V. litorea plastids. Higher levels of FtsH were also evident in cycloheximide-treated cells during recovery from photoinhibition. Charge recombination in PSII of V. litorea was found to be fine-tuned to produce only small quantities of singlet oxygen, and the plastids also contained reactive oxygen species-protective compounds. Our results support the view that the genetic characteristics of the plastids are crucial in creating a photosynthetic sea slug. The plastid’s autonomous repair machinery is likely enhanced by low singlet oxygen production and elevated expression of FtsH.</p

Red and Problematic Green Phylogenetic Signals among Thousands of Nuclear Genes from the Photosynthetic and Apicomplexa-Related Chromera velia

The photosynthetic and basal apicomplexan Chromera velia was recently described, expanding the membership of this otherwise nonphotosynthetic group of parasite protists. Apicomplexans are alveolates with secondary plastids of red algal origin, but the evolutionary history of their nuclear genes is still actively discussed. Using deep sequencing of expressed genes, we investigated the phylogenetic affinities of a stringent filtered set of 3,151 expressed sequence tag-contigs by generating clusters with eukaryotic homologs and constructing phylogenetic trees and networks. The phylogenetic positioning of this alveolate alga was determined and sets of phyla-specific proteins extracted. Phylogenetic trees provided conflicting signals, with 444 trees grouping C. velia with the apicomplexans but 354 trees grouping C. velia with the alveolate oyster pathogen Perkinsus marinus, the latter signal being reinforced from the analysis of shared genes and overall sequence similarity. Among the 513 C. velia nuclear genes that reflect a photosynthetic ancestry and for which nuclear homologs were available both from red and green lineages, 263 indicated a red photosynthetic ancestry, whereas 250 indicated a green photosynthetic ancestry. The same 1:1 signal ratio was found among the putative 255 nuclear-encoded plastid proteins identified. This finding of red and green signals for the alveolate mirrors the result observed in the heterokont lineage and supports a common but not necessarily single origin for the plastid in heterokonts and alveolates. The inference of green endosymbiosis preceding red plastid acquisition in these lineages leads to worryingly complicated evolutionary scenarios, prompting the search for other explanations for the green phylogenetic signal and the amount of hosts involved

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies