75 research outputs found

    Chlamydial contribution to anaerobic metabolism during eukaryotic evolution

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    The origin of eukaryotes is a major open question in evolutionary biology. Multiple hypotheses posit that eukaryotes likely evolved from a syntrophic relationship between an archaeon and an alphaproteobacterium based on H-2 exchange. However, there are no strong indications that modern eukaryotic H-2 metabolism originated from archaea or alphaproteobacteria. Here, we present evidence for the origin of H-2 metabolism genes in eukaryotes from an ancestor of the Anoxychlamydiales-a group of anaerobic chlamydiae, newly described here, from marine sediments. Among Chlamydiae, these bacteria uniquely encode genes for H-2 metabolism and other anaerobiosis-associated pathways. Phylogenetic analyses of several components of H-2 metabolism reveal that Anoxychlamydiales homologs are the closest relatives to eukaryotic sequences. We propose that an ancestor of the Anoxychlamydiales contributed these key genes during the evolution of eukaryotes, supporting a mosaic evolutionary origin of eukaryotic metabolism

    Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival

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    Recent evidence suggests CML stem cells are insensitive to kinase inhibitors and responsible for minimal residual disease in treated patients. We investigated whether CML stem cells, in a transgenic mouse model of CML-like disease or derived from patients, are dependent on Bcr-Abl. In the transgenic model, following re-transplantation, donor-derived CML stem cells in which Bcr-Abl expression had been induced and subsequently shut off, were able to persist in vivo and re-initiate leukemia in secondary recipients upon Bcr-Abl re-expression. Bcr-Abl knockdown in human CD34+ CML cells cultured for 12 days in physiological growth factors achieved partial inhibition of Bcr-Abl and downstream targets p-CrkL and p-STAT5, inhibition of proliferation and colony forming cells, but no reduction of input cells. The addition of dasatinib further inhibited p-CrkL and p-STAT5, yet only reduced input cells by 50%. Complete growth factor withdrawal plus dasatinib further reduced input cells to 10%, however the surviving fraction was enriched for primitive leukemic cells capable of growth in long-term culture initiating cell assay and expansion upon removal of dasatinib and addition of growth factors. Together these data suggest that CML stem cell survival is Bcr-Abl kinase independent and suggest curative approaches in CML must focus on kinase-independent mechanisms of resistance

    Detection of Water Vapor in the Photosphere of Arcturus

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    We report detections of pure rotation lines of OH and H2O in the K1.5 III red-giant star Arcturus (alpha Bootis) using high-resolution, infrared spectra covering the regions 806-822 cm-1 (12.2-12.4 um) and 884-923 cm-1 (10.8-11.3 um). Arcturus is the hottest star yet to show water-vapor features in its disk-averaged spectrum. We argue that the water vapor lines originate from the photosphere, albeit in the outer layers. We are able to predict the observed strengths of OH and H2O lines satisfactorily after lowering the temperature structure of the very outer parts of the photosphere (log tau_500=-3.8 and beyond) compared to a flux-constant, hydrostatic, standard MARCS model photosphere. Our new model is consistently calculated including chemical equilibrium and radiative transfer from the given temperature structure. Possible reasons for a temperature decrease in the outer-most parts of the photosphere and the assumed break-down of the assumptions made in classical model-atmosphere codes are discussed.Comment: To appear in ApJ. See also http://www.astro.uu.se/~ryde/ART

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Microbial diversity of Loki’s Castle black smokers at the Arctic Mid-Ocean Ridge

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    Hydrothermal vent systems harbor rich microbial communities ranging from aerobic mesophiles to anaerobic hyperthermophiles. Among these, members of the archaeal domain are prevalent in microbial communities in the most extreme environments, partly because of their temperature-resistant and robust membrane lipids. In this study, we use geochemical and molecular microbiological methods to investigate the microbial diversity in black smoker chimneys from the newly discovered Loki's Castle hydrothermal vent field on the Arctic Mid-Ocean Ridge (AMOR) with vent fluid temperatures of 310–320 °C and pH of 5.5. Archaeal glycerol dialkyl glycerol tetraether lipids (GDGTs) and H-shaped GDGTs with 0–4 cyclopentane moieties were dominant in all sulfide samples and are most likely derived from both (hyper)thermophilic Euryarchaeota and Crenarchaeota. Crenarchaeol has been detected in low abundances in samples derived from the chimney exterior indicating the presence of Thaumarchaeota at lower ambient temperatures. Aquificales and members of the Epsilonproteobacteria were the dominant bacterial groups detected. Our observations based on the analysis of 16S rRNA genes and biomarker lipid analysis provide insight into microbial communities thriving within the porous sulfide structures of active and inactive deep-sea hydrothermal vents. Microbial cycling of sulfur, hydrogen, and methane by archaea in the chimney interior and bacteria in the chimney exterior may be the prevailing biogeochemical processes in this system

    Virus Genomes from Deep Sea Sediments Expand the Ocean Megavirome and Support Independent Origins of Viral Gigantism

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    The nucleocytoplasmic large DNA viruses (NCLDV) of eukaryotes (proposed order, “Megavirales”) include the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Marseilleviridae, and Mimiviridae, as well as still unclassified pithoviruses, pandoraviruses, molliviruses, and faustoviruses. Several of these virus groups include giant viruses, with genome and particle sizes exceeding those of many bacterial and archaeal cells. We explored the diversity of the NCLDV in deep sea sediments from the Loki’s Castle hydrothermal vent area. Using metagenomics, we reconstructed 23 high-quality genomic bins of novel NCLDV, 15 of which are related to pithoviruses, 5 to marseilleviruses, 1 to iridoviruses, and 2 to klosneuviruses. Some of the identified pithovirus-like and marseillevirus-like genomes belong to deep branches in the phylogenetic tree of core NCLDV genes, substantially expanding the diversity and phylogenetic depth of the respective groups. The discovered viruses, including putative giant members of the family Marseilleviridae, have a broad range of apparent genome sizes, in agreement with the multiple, independent origins of gigantism in different branches of the NCLDV. Phylogenomic analysis reaffirms the monophyly of the pithovirus-iridovirus-marseillevirus branch of the NCLDV. Similarly to other giant viruses, the pithovirus-like viruses from Loki’s Castle encode translation systems components. Phylogenetic analysis of these genes indicates a greater bacterial contribution than had been detected previously. Genome comparison suggests extensive gene exchange between members of the pithovirus-like viruses and Mimiviridae. Further exploration of the genomic diversity of Megavirales in additional sediment samples is expected to yield new insights into the evolution of giant viruses and the composition of the ocean megavirome. Importance: Genomics and evolution of giant viruses are two of the most vigorously developing areas of virus research. Lately, metagenomics has become the main source of new virus genomes. Here we describe a metagenomic analysis of the genomes of large and giant viruses from deep sea sediments. The assembled new virus genomes substantially expand the known diversity of the nucleocytoplasmic large DNA viruses of eukaryotes. The results support the concept of independent evolution of giant viruses from smaller ancestors in different virus branches
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