388 research outputs found

    Phylogenetic multi-locus codon models and molecular clocks reveal the monophyly of haematophagous reduviid bugs and their evolution at the formation of South America.

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    We previously constructed a single molecular clock to date insect evolution that remains a cornerstone within entomological dating. The insect clock predicts that triatomine bugs, the vectors of South American trypanosomiasis, originated with the formation of South America. We addressed this hypothesis using the insectivorous reduviid bugs and their phylogenetic relationship with the haematophagous reduviid bugs, as well as their biogeographic distribution. Putative paraphyly or monophyly of Triatominae, by non-haematophagous reduviids, have both previously been hypothesized and identified. We sampled a broad range of predatory reduviids, viz. Ectrichodiinae, Emesinae, Hammacerinae, Harpactorinae, Reduviinae, Salyavatinae, Steniopodainae and Vesciinae, including both New World and Old World representatives and sequenced the nuclear 28S ribosomal gene locus and the mitochondrial loci 5' cytochrome oxidase 1 (cox1 [COI]), cox1 3', cytochrome oxidase 2 (cox2 [COII]) and cytochrome oxidase b (cob [cytb]). Robust evidence for the monophyly of Triatominae was observed in 5/5 loci using codon/nucleotide (28S) based maximum likelihood phylogenies, 3/5 loci using codon-based Bayesian phylogenies and in cox2 using amino acid Bayesian phylogenies. Several South American members of the Reduviinae, that are morphologically and phylogenetically a sister group to triatomine bugs, have a modal divergence date with the Triatominae of 109-107 million years ago (MYA). This creates a scenario where the closest (non-haematophagous) ancestor to triatomine bugs evolved immediately prior to the breakup of Gondwanaland whilst the triatomine bugs evolved 95MYA, putatively linking the origin of haematophagous behaviour to the origin of South America and in particular infers a delayed onset to the evolution of haematophagy. The placement of the enigmatic tribe Bolboderini as an ingroup to the Triatominae monophyly, confirms the 95MYA node as the most ancient in the subfamily

    Trypanosomes are monophyletic: evidence from genes for glyceraldehyde phosphate dehydrogenase and small subunit ribosomal RNA.

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    The genomes of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major have been sequenced, but the phylogenetic relationships of these three protozoa remain uncertain. We have constructed trypanosomatid phylogenies based on genes for glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) and small subunit ribosomal RNA (SSU rRNA). Trees based on gGAPDH nucleotide and amino acid sequences (51 taxa) robustly support monophyly of genus Trypanosoma, which is revealed to be a relatively late-evolving lineage of the family Trypanosomatidae. Other trypanosomatids, including genus Leishmania, branch paraphyletically at the base of the trypanosome clade. On the other hand, analysis of the SSU rRNA gene data produced equivocal results, as trees either robustly support or reject monophyly depending on the range of taxa included in the alignment. We conclude that the SSU rRNA gene is not a reliable marker for inferring deep level trypanosome phylogeny. The gGAPDH results support the hypothesis that trypanosomes evolved from an ancestral insect parasite, which adapted to a vertebrate/insect transmission cycle. This implies that the switch from terrestrial insect to aquatic leech vectors for fish and some amphibian trypanosomes was secondary. We conclude that the three sequenced pathogens, T. brucei, T. cruzi and L. major, are only distantly related and have distinct evolutionary histories

    Trypanosoma cruzi IIc: phylogenetic and phylogeographic insights from sequence and microsatellite analysis and potential impact on emergent Chagas disease.

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    Trypanosoma cruzi, the etiological agent of Chagas disease, is highly genetically diverse. Numerous lines of evidence point to the existence of six stable genetic lineages or DTUs: TcI, TcIIa, TcIIb, TcIIc, TcIId, and TcIIe. Molecular dating suggests that T. cruzi is likely to have been an endemic infection of neotropical mammalian fauna for many millions of years. Here we have applied a panel of 49 polymorphic microsatellite markers developed from the online T. cruzi genome to document genetic diversity among 53 isolates belonging to TcIIc, a lineage so far recorded almost exclusively in silvatic transmission cycles but increasingly a potential source of human infection. These data are complemented by parallel analysis of sequence variation in a fragment of the glucose-6-phosphate isomerase gene. New isolates confirm that TcIIc is associated with terrestrial transmission cycles and armadillo reservoir hosts, and demonstrate that TcIIc is far more widespread than previously thought, with a distribution at least from Western Venezuela to the Argentine Chaco. We show that TcIIc is truly a discrete T. cruzi lineage, that it could have an ancient origin and that diversity occurs within the terrestrial niche independently of the host species. We also show that spatial structure among TcIIc isolates from its principal host, the armadillo Dasypus novemcinctus, is greater than that among TcI from Didelphis spp. opossums and link this observation to differences in ecology of their respective niches. Homozygosity in TcIIc populations and some linkage indices indicate the possibility of recombination but cannot yet be effectively discriminated from a high genome-wide frequency of gene conversion. Finally, we suggest that the derived TcIIc population genetic data have a vital role in determining the origin of the epidemiologically important hybrid lineages TcIId and TcIIe

    The ecotopes and evolution of triatomine bugs (triatominae) and their associated trypanosomes

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    Triatomine bug species such as Microtriatoma trinidadensis, Eratyrus mucronatus, Belminus herreri, Panstrongylus lignarius, and Triatoma tibiamaculata are exquisitely adapted to specialist niches. This suggests a long evolutionary history, as well as the recent dramatic spread a few eclectic, domiciliated triatomine species. Virtually all species of the genus Rhodnius are primarily associated with palms. The genus Panstrongylus is predominantly associated with burrows and tree cavities and the genus Triatoma with terrestrial rocky habitats or rodent burrows. Two major sub-divisions have been defined within the species Trypanosoma cruzi, as T. cruzi 1 (Z1) and T. cruzi 2 (Z2). The affinities of a third group (Z3) are uncertain. Host and habitat associations lead us to propose that T. cruzi 1 (Z1) has evolved in an arboreal, palm tree habitat with the triatomine tribe Rhodniini, in association with the opossum Didelphis. Similarly we propose that T. cruzi (Z2) and Z3 evolved in a terrestrial habitat in burrows and in rocky locations with the triatomine tribe Triatomini, in association with edentates, and/or possibly ground dwelling marsupials. Both sub-divisions of T. cruzi may have been contemporary in South America up to 65 million years ago. Alternatively, T. cruzi 2 (Z2) may have evolved more recently from T. cruzi 1 (Z1) by host transfers into rodents, edentates, and primates. We have constructed a molecular phylogeny of haematophagous vectors, including triatomine bugs, which suggests that faecal transmission of trypanosomes may be the ancestral route. A molecular clock phylogeny suggests that Rhodnius and Triatoma diverged before the arrival, about 40 million years ago, of bats and rodents into South America

    GTB – An Online Genome Tolerance Browser

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    BACKGROUND: Accurate methods capable of predicting the impact of single nucleotide variants (SNVs) are assuming ever increasing importance. There exists a plethora of in silico algorithms designed to help identify and prioritize SNVs across the human genome for further investigation. However, no tool exists to visualize the predicted tolerance of the genome to mutation, or the similarities between these methods. RESULTS: We present the Genome Tolerance Browser (GTB, http://gtb.biocompute.org.uk): an online genome browser for visualizing the predicted tolerance of the genome to mutation. The server summarizes several in silico prediction algorithms and conservation scores: including 13 genome-wide prediction algorithms and conservation scores, 12 non-synonymous prediction algorithms and four cancer-specific algorithms. CONCLUSION: The GTB enables users to visualize the similarities and differences between several prediction algorithms and to upload their own data as additional tracks; thereby facilitating the rapid identification of potential regions of interest. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-1436-4) contains supplementary material, which is available to authorized users

    Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve

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    ObjectiveTo assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years.MethodsPatients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated.ResultsPatients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 ± 3.9 mm Hg to 103.5 ± 4.6 mm Hg (P < .00001) and from 87.6 ± 4.3 mm Hg to 94.0 ± 4.5 mm Hg (P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group (P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease.ConclusionsCarotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely

    Dynamic Format Selection of Media Content

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    Disclosed herein is an improved mechanism for dynamic format selection of media content. The mechanism can use a machine learning model to select a format (e.g., a playback resolution) for providing media content based on information available at the time when the request for providing the media content is received. Such information can include, for example, location information (e.g., the geographic location of a user device that is presenting the media content), account information (e.g., previously selected media content items, watch time statistical information, subscription information, etc.), and/or network condition information (e.g., current egress traffic from one or more servers associated with the media streaming service)

    Superior epigastric artery pseudoaneurysm- a rare complication of chest drain insertion in coronary artery bypass grafting

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    BACKGROUND: Although chest drain insertion during coronary artery bypass grafting is a fairly standard procedure, however it may result in extremely rare complications. CASE PRESENTATION: This is the first case being reported that demonstrates a pseudoaneurysm of superior epigastric artery resulting from chest drain insertion following coronary artery bypass grafting. CONCLUSION: Adequate caution should be used along with good understanding of the anatomical landmarks during apparently simple and standard operative procedures

    An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

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    Background: Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results: We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions: FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome
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