Genetic Evidence for a Mitochondriate Ancestry in the ‘Amitochondriate’ Flagellate Trimastix pyriformis

Most modern eukaryotes diverged from a common ancestor that contained the α-proteobacterial endosymbiont that gave rise to mitochondria. The ‘amitochondriate’ anaerobic protist parasites that have been studied to date, such as Giardia and Trichomonas harbor mitochondrion-related organelles, such as mitosomes or hydrogenosomes. Yet there is one remaining group of mitochondrion-lacking flagellates known as the Preaxostyla that could represent a primitive ‘pre-mitochondrial’ lineage of eukaryotes. To test this hypothesis, we conducted an expressed sequence tag (EST) survey on the preaxostylid flagellate Trimastix pyriformis, a poorly-studied free-living anaerobe. Among the ESTs we detected 19 proteins that, in other eukaryotes, typically function in mitochondria, hydrogenosomes or mitosomes, 12 of which are found exclusively within these organelles. Interestingly, one of the proteins, aconitase, functions in the tricarboxylic acid cycle typical of aerobic mitochondria, whereas others, such as pyruvate:ferredoxin oxidoreductase and [FeFe] hydrogenase, are characteristic of anaerobic hydrogenosomes. Since Trimastix retains genetic evidence of a mitochondriate ancestry, we can now say definitively that all known living eukaryote lineages descend from a common ancestor that had mitochondria

Transcriptomic profiling of host-parasite interactions in the microsporidian <i>Trachipleistophora hominis</i>

BACKGROUND: Trachipleistophora hominis was isolated from an HIV/AIDS patient and is a member of a highly successful group of obligate intracellular parasites. METHODS: Here we have investigated the evolution of the parasite and the interplay between host and parasite gene expression using transcriptomics of T. hominis-infected rabbit kidney cells. RESULTS: T. hominis has about 30 % more genes than small-genome microsporidians. Highly expressed genes include those involved in growth, replication, defence against oxidative stress, and a large fraction of uncharacterised genes. Chaperones are also highly expressed and may buffer the deleterious effects of the large number of non-synonymous mutations observed in essential T. hominis genes. Host expression suggests a general cellular shutdown upon infection, but ATP, amino sugar and nucleotide sugar production appear enhanced, potentially providing the parasite with substrates it cannot make itself. Expression divergence of duplicated genes, including transporters used to acquire host metabolites, demonstrates ongoing functional diversification during microsporidian evolution. We identified overlapping transcription at more than 100 loci in the sparse T. hominis genome, demonstrating that this feature is not caused by genome compaction. The detection of additional transposons of insect origin strongly suggests that the natural host for T. hominis is an insect. CONCLUSIONS: Our results reveal that the evolution of contemporary microsporidian genomes is highly dynamic and innovative. Moreover, highly expressed T. hominis genes of unknown function include a cohort that are shared among all microsporidians, indicating that some strongly conserved features of the biology of these enormously successful parasites remain uncharacterised. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1989-z) contains supplementary material, which is available to authorized users

Cap integration in spectral gravity forward modelling: near- and far-zone gravity effects via Molodensky’s truncation coefficients

Spectral gravity forward modelling is a technique that converts a band-limited topography into its implied gravitational field. This conversion implicitly relies on global integration of topographic masses. In this paper, a modification of the spectral technique is presented that provides gravity effects induced only by the masses located inside or outside a spherical cap centred at the evaluation point. This is achieved by altitude-dependent Molodensky’s truncation coefficients, for which we provide infinite series expansions and recurrence relations with a fixed number of terms. Both representations are generalized for an arbitrary integer power of the topography and arbitrary radial derivative. Because of the altitude-dependency of the truncation coefficients, a straightforward synthesis of the near- and far-zone gravity effects at dense grids on irregular surfaces (e.g. the Earth’s topography) is computationally extremely demanding. However, we show that this task can be efficiently performed using an analytical continuation based on the gradient approach, provided that formulae for radial derivatives of the truncation coefficients are available. To demonstrate the new cap-modified spectral technique, we forward model the Earth’s degree-360 topography, obtaining near- and far-zone effects on gravity disturbances expanded up to degree 3600. The computation is carried out on the Earth’s surface and the results are validated against an independent spatial-domain Newtonian integration ((Formula presented.) RMS agreement). The new technique is expected to assist in mitigating the spectral filter problem of residual terrain modelling and in the efficient construction of full-scale global gravity maps of highest spatial resolution

Everolimus in heart transplantation: an update.

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

To investigate immuno-chemotherapy for elderly immuno-competent patients (. 65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m(2), days 1, 15, 29), high-dose methotrexate (3 g/m(2) days 2, 16, 30), procarbazine (60 mg/m(2) days 2-11) and lomustine (110 mg/m(2), day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less. grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies