Publications by authors named "Roger A"

392 Publications

Evolution: Reconstructing the Timeline of Eukaryogenesis.

Curr Biol 2021 Feb;31(4):R193-R196

Institute of Evolutionary Biology (CSIC-UPF), Barcelona 08003, Spain.

Timing the events in the evolution of eukaryotic cells is crucial to understanding this major transition. A recent study reconstructs the origins of thousands of gene families ancestral to eukaryotes and, using a controversial approach, aims to order the events of eukaryogenesis.
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http://dx.doi.org/10.1016/j.cub.2020.12.035DOI Listing
February 2021

Which adjuvant treatment for patients with BRAF-mutant cutaneous melanoma?

Ann Dermatol Venereol 2021 Feb 9. Epub 2021 Feb 9.

Department of General and Oncologic Dermatology, Ambroise-Paré hospital, AP-HP, Boulogne-Billancourt, France; Research unit EA4340 "Biomarkers and clinical trials in oncology and onco-hematology", Versailles-Saint-Quentin-en-Yvelines University, Paris-Saclay University, France.

Treatment of patients with melanoma has considerably improved over the past decade and more recently with adjuvant therapies for patients with American Joint Committee on Cancer (AJCC) stage III (loco-regional metastases) or IV (distant metastases) totally resected melanoma, in order to prevent recurrence. In the adjuvant setting, two options are available to patients with BRAF-mutant AJCC stage III totally resected melanoma: anti-PD-1 blockers (nivolumab or pembrolizumab) or BRAF plus MEK inhibitors (dabrafenib plus trametinib). In the absence of comparative studies, it is difficult to determine which of these options is best. Our aim was to review published studies focusing on the management of patients with BRAF-mutant melanoma in the adjuvant setting. We also reviewed the main clinical trials of BRAF plus MEK inhibitors and immunotherapy in advanced (i.e. unresectable metastatic) BRAF-mutant melanoma in an attempt to identify results potentially affecting the management of patients on adjuvants. More adverse events are observed with targeted therapy, but all resolve rapidly upon drug discontinuation, whereas with immune checkpoint blockers some adverse events may persist. New therapeutic strategies are emerging, notably neoadjuvant therapies for stage III patients and adjuvant therapies for stage II patients; the place of the adjuvant strategy amidst all these options will soon be re-evaluated. The choice of adjuvant treatment could influence the choice of subsequent treatments in neo-adjuvant or metastatic settings. This review will lead clinicians to a better understanding of the different adjuvant treatments available for patients with totally resected AJCC stage III and IV BRAF-mutant melanoma before considering subsequent treatment strategies.
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http://dx.doi.org/10.1016/j.annder.2020.11.006DOI Listing
February 2021

The Mastigamoeba balamuthi genome and the nature of the free-living ancestor of Entamoeba.

Mol Biol Evol 2021 Feb 2. Epub 2021 Feb 2.

Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Průmyslová 595 25242 Vestec, Czech Republic.

The transition of free-living organisms to parasitic organisms is a mysterious process that occurs in all major eukaryotic lineages. Parasites display seemingly unique features associated with their pathogenicity; however, it is important to distinguish ancestral preconditions to parasitism from truly new parasite-specific functions. Here, we sequenced the genome and transcriptome of anaerobic free-living M. balamuthi and performed phylogenomic analysis of four related members of the Archamoebae, including Entamoeba histolytica, an important intestinal pathogen of humans. We aimed to trace gene histories throughout the adaptation of the aerobic ancestor of Archamoebae to anaerobiosis and throughout the transition from a free-living to a parasitic lifestyle. These events were associated with massive gene losses that, in parasitic lineages, resulted in a reduction in structural features, complete losses of some metabolic pathways, and a reduction in metabolic complexity. By reconstructing the features of the common ancestor of Archamoebae, we estimated preconditions for the evolution of parasitism in this lineage. The ancestor could apparently form chitinous cysts, possessed proteolytic enzyme machinery, compartmentalized the sulfate activation pathway in mitochondrion-related organelles, and possessed the components for anaerobic energy metabolism. After the split of Entamoebidae, this lineage gained genes encoding surface membrane proteins that are involved in host-parasite interactions. In contrast, gene gains identified in the M. balamuthi lineage were predominantly associated with polysaccharide catabolic processes. A phylogenetic analysis of acquired genes suggested an essential role of lateral gene transfer in parasite evolution (Entamoeba) and in adaptation to anaerobic aquatic sediments (Mastigamoeba).
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http://dx.doi.org/10.1093/molbev/msab020DOI Listing
February 2021

Long Branch Attraction Biases in Phylogenetics.

Syst Biol 2021 Feb 2. Epub 2021 Feb 2.

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.

Long branch attraction is a prevalent form of bias in phylogenetic estimation but the reasons for it are only partially understood. We argue here that it is largely due to differences in the sizes of the model spaces corresponding to different trees. Trees with long branches together allow much more flexible internal branch-length parameter estimation. Consequently, although each tree has the same number of parameters, trees with long branches together have larger effective model spaces. The problem of long branch attraction becomes particularly pronounced with partitioned data. Formulation of tree estimation as model selection leads us to propose bootstrap bias corrections as cross-checks on estimation when long branches end up being estimated together.
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http://dx.doi.org/10.1093/sysbio/syab001DOI Listing
February 2021

Industrial carbon dioxide capture and utilization: state of the art and future challenges.

Chem Soc Rev 2020 Dec 19;49(23):8584-8686. Epub 2020 Oct 19.

College of Environmental Science and Engineering, Beijing Forestry University, 35 Qinghua East Road, Haidian District, Beijing 100083, P. R. China.

Dramatically increased CO concentration from several point sources is perceived to cause severe greenhouse effect towards the serious ongoing global warming with associated climate destabilization, inducing undesirable natural calamities, melting of glaciers, and extreme weather patterns. CO capture and utilization (CCU) has received tremendous attention due to its significant role in intensifying global warming. Considering the lack of a timely review on the state-of-the-art progress of promising CCU techniques, developing an appropriate and prompt summary of such advanced techniques with a comprehensive understanding is necessary. Thus, it is imperative to provide a timely review, given the fast growth of sophisticated CO capture and utilization materials and their implementation. In this work, we critically summarized and comprehensively reviewed the characteristics and performance of both liquid and solid CO adsorbents with possible schemes for the improvement of their CO capture ability and advances in CO utilization. Their industrial applications in pre- and post-combustion CO capture as well as utilization were systematically discussed and compared. With our great effort, this review would be of significant importance for academic researchers for obtaining an overall understanding of the current developments and future trends of CCU. This work is bound to benefit researchers in fields relating to CCU and facilitate the progress of significant breakthroughs in both fundamental research and commercial applications to deliver perspective views for future scientific and industrial advances in CCU.
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http://dx.doi.org/10.1039/d0cs00025fDOI Listing
December 2020

Anaphylaxis Induced By Beer.

J Investig Allergol Clin Immunol 2020 Sep 15. Epub 2020 Sep 15.

Allergy Section, Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona, Badalona.

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http://dx.doi.org/10.18176/jiaci.0643DOI Listing
September 2020

Lateral Gene Transfer Mechanisms and Pan-genomes in Eukaryotes.

Trends Parasitol 2020 11 19;36(11):927-941. Epub 2020 Aug 19.

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada; Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address:

Lateral gene transfer (LGT) is well known as an important driver of genome evolution in bacteria and archaea, but its importance in eukaryote evolution has yet to be fully elucidated. There is now abundant evidence indicating that LGT has played a role in the adaptation of eukaryotes to new environments and conditions, including host-parasite interactions. However, the mechanisms and frequency of LGT across the tree of eukaryotes remain poorly understood. Here we review evidence for known and potential mechanisms of LGT into diverse eukaryote lineages with a particular focus on protists, and we discuss trends emerging from recently reported examples. We also explore the potential role of LGT in generating 'pan-genomes' in diverse eukaryotic species.
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http://dx.doi.org/10.1016/j.pt.2020.07.014DOI Listing
November 2020

Clinical trial to assess tolerability and subrogate efficacy effects of an abbreviated schedule with house dust mites mixture subcutaneous immunotherapy.

Eur Ann Allergy Clin Immunol 2021 03 1;53(2):67-74. Epub 2021 Mar 1.

Department of R/D, ROXALL Medicina España S.A., Zamudio, Spain.

Summary: To evaluate the tolerability and efficacy of mixture subcutaneous immunotherapy (SCIT). Patients received an abbreviated build-up schedule. The aims were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Out of 289 administrations, 17% elicited any clinically relevant adverse reaction. Most of them were local reactions (LR) (9.4%) and the rest (7.6%) were systemic. Significant increases in sIgG and sIgG4 were detected in serum samples. Cutaneous reactivity decreased significantly. SCIT with house dust mites mixture of ROXALL Medicina España S.A. seems to have an acceptable tolerability profile, induces blocking IgG and decreases skin reactivity.
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http://dx.doi.org/10.23822/EurAnnACI.1764-1489.140DOI Listing
March 2021

The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome.

BMC Biol 2020 03 2;18(1):22. Epub 2020 Mar 2.

Département de Biochimie and Robert-Cedergren Center for Bioinformatics and Genomics, Université de Montréal, Montréal, QC, Canada.

Background: Comparative analyses have indicated that the mitochondrion of the last eukaryotic common ancestor likely possessed all the key core structures and functions that are widely conserved throughout the domain Eucarya. To date, such studies have largely focused on animals, fungi, and land plants (primarily multicellular eukaryotes); relatively few mitochondrial proteomes from protists (primarily unicellular eukaryotic microbes) have been examined. To gauge the full extent of mitochondrial structural and functional complexity and to identify potential evolutionary trends in mitochondrial proteomes, more comprehensive explorations of phylogenetically diverse mitochondrial proteomes are required. In this regard, a key group is the jakobids, a clade of protists belonging to the eukaryotic supergroup Discoba, distinguished by having the most gene-rich and most bacteria-like mitochondrial genomes discovered to date.

Results: In this study, we assembled the draft nuclear genome sequence for the jakobid Andalucia godoyi and used a comprehensive in silico approach to infer the nucleus-encoded portion of the mitochondrial proteome of this protist, identifying 864 candidate mitochondrial proteins. The A. godoyi mitochondrial proteome has a complexity that parallels that of other eukaryotes, while exhibiting an unusually large number of ancestral features that have been lost particularly in opisthokont (animal and fungal) mitochondria. Notably, we find no evidence that the A. godoyi nuclear genome has or had a gene encoding a single-subunit, T3/T7 bacteriophage-like RNA polymerase, which functions as the mitochondrial transcriptase in all eukaryotes except the jakobids.

Conclusions: As genome and mitochondrial proteome data have become more widely available, a strikingly punctuate phylogenetic distribution of different mitochondrial components has been revealed, emphasizing that the pathways of mitochondrial proteome evolution are likely complex and lineage-specific. Unraveling this complexity will require comprehensive comparative analyses of mitochondrial proteomes from a phylogenetically broad range of eukaryotes, especially protists. The systematic in silico approach described here offers a valuable adjunct to direct proteomic analysis (e.g., via mass spectrometry), particularly in cases where the latter approach is constrained by sample limitation or other practical considerations.
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http://dx.doi.org/10.1186/s12915-020-0741-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050145PMC
March 2020

Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy.

Int J Cancer 2020 Sep 28;147(6):1707-1714. Epub 2020 Feb 28.

Department of General and Oncologic Dermatology, Ambroise-Paré Hospital, APHP & EA 4340 Biomarkers in Cancerology and Hemato-Oncology, UVSQ, Université Paris-Saclay, Paris, France.

Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3-5 sessions, 20-26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed.
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http://dx.doi.org/10.1002/ijc.32934DOI Listing
September 2020

Real-life effect of a microcrystalline tyrosine adjuvanted mite immunotherapy in patients with allergic rhinitis.

Immunotherapy 2020 01 8;12(1):53-62. Epub 2020 Jan 8.

Allergy Therapeutics Ibérica, Sant Joan Despí, Barcelona, Spain.

Evaluate the effectiveness and safety of immunotherapy with Acarovac Plus in a 1-year prospective multicentered real-life study. A total of 118 adults with allergic rhinitis sensitized to received subcutaneous immunotherapy with Acarovac Plus. Treatment outcomes were evaluated at baseline, 6 months and 1 year after treatment initiation. Primary end point was the evolution of the combined symptom and medication score. Secondary end points included other effectiveness outcomes and measurement of product tolerability. Acarovac Plus induced significant improvements in primary and secondary end points after 6 months compared with baseline. These differences persisted after 1 year of treatment (p < 0.001; baseline vs 1 year): combined symptom and medication score (1.60 vs 0.79). No serious adverse events were recorded. Acarovac Plus for 1 year was effective and well tolerated in a real-life setting.
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http://dx.doi.org/10.2217/imt-2019-0205DOI Listing
January 2020

On the Use of Information Criteria for Model Selection in Phylogenetics.

Mol Biol Evol 2020 02;37(2):549-562

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.

The information criteria Akaike information criterion (AIC), AICc, and Bayesian information criterion (BIC) are widely used for model selection in phylogenetics, however, their theoretical justification and performance have not been carefully examined in this setting. Here, we investigate these methods under simple and complex phylogenetic models. We show that AIC can give a biased estimate of its intended target, the expected predictive log likelihood (EPLnL) or, equivalently, expected Kullback-Leibler divergence between the estimated model and the true distribution for the data. Reasons for bias include commonly occurring issues such as small edge-lengths or, in mixture models, small weights. The use of partitioned models is another issue that can cause problems with information criteria. We show that for partitioned models, a different BIC correction is required for it to be a valid approximation to a Bayes factor. The commonly used AICc correction is not clearly defined in partitioned models and can actually create a substantial bias when the number of parameters gets large as is the case with larger trees and partitioned models. Bias-corrected cross-validation corrections are shown to provide better approximations to EPLnL than AIC. We also illustrate how EPLnL, the estimation target of AIC, can sometimes favor an incorrect model and give reasons for why selection of incorrectly under-partitioned models might be desirable in partitioned model settings.
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http://dx.doi.org/10.1093/molbev/msz228DOI Listing
February 2020

The New Tree of Eukaryotes.

Trends Ecol Evol 2020 01 9;35(1):43-55. Epub 2019 Oct 9.

Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, NS, Canada; Department of Biology, Dalhousie University, Halifax, NS, Canada. Electronic address:

For 15 years, the eukaryote Tree of Life (eToL) has been divided into five to eight major groupings, known as 'supergroups'. However, the tree has been profoundly rearranged during this time. The new eToL results from the widespread application of phylogenomics and numerous discoveries of major lineages of eukaryotes, mostly free-living heterotrophic protists. The evidence that supports the tree has transitioned from a synthesis of molecular phylogenetics and biological characters to purely molecular phylogenetics. Most current supergroups lack defining morphological or cell-biological characteristics, making the supergroup label even more arbitrary than before. Going forward, the combination of traditional culturing with maturing culture-free approaches and phylogenomics should accelerate the process of completing and resolving the eToL at its deepest levels.
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http://dx.doi.org/10.1016/j.tree.2019.08.008DOI Listing
January 2020

Interrater Agreement Between Critical Care Providers for Background Classification and Seizure Detection After Implementation of Amplitude-Integrated Electroencephalography in Neonates, Infants, and Children.

J Clin Neurophysiol 2020 May;37(3):259-262

Pediatric Intensive Care Unit, University Hospital, Nantes, France.

Purposes: Amplitude-integrated EEG (aEEG) has been widely developed in neonatal intensive care unit, but few studies focused on pediatric intensive care unit. Furthermore, reliability of aEEG under real-life conditions is unknown.

Methods: Participants were nurses from a 12-bed pediatric intensive care unit in a referral university hospital in France. Amplitude EEG was implemented after standardized training, including e-learning course, individual feedback and bedside teaching concerning monitoring installation, background classification patterns recognition, artefact analysis, and seizure detection. The primary judgment criterion was the agreement (Cohen Kappa) between nurses and aEEG experts for the detection of abnormal aEEG traces (moderately or severely altered background pattern according to Hellström-Westas classification and/or seizure activity).

Results: During the study period, 196 consecutives traces from 79 patients were analyzed by 51 nurses. According to expert's classification, 53% of traces were abnormal, including 17.5% of severely abnormal traces (severely altered traces and/or seizure activity) and 14% exhibiting seizure activity. Moderate agreement between experts and nurses was found for detection of any abnormal trace (k = 0.53; 95% confidence interval [CI]: 0.39-0.67). Substantial agreement was found for severely altered traces (k = 0.71; 95% CI: 0.57-0.85). Finally, fair agreement was found for seizure detection (irrespective of background classification, k = 0.40; 95% CI: 0.25-0.54).

Conclusions: These results suggest that aEEG monitoring may be implemented in routine nursing care in pediatric intensive care unit. Further training courses are needed to enhance nurses' skill in detecting seizures activity at the bedside.
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http://dx.doi.org/10.1097/WNP.0000000000000634DOI Listing
May 2020

The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion.

Mol Biol Evol 2019 10;36(10):2292-2312

Department of Parasitology, BIOCEV, Faculty of Science, Charles University, Vestec, Czech Republic.

The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
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http://dx.doi.org/10.1093/molbev/msz147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759080PMC
October 2019

A natural toroidal microswimmer with a rotary eukaryotic flagellum.

Nat Microbiol 2019 10 10;4(10):1620-1626. Epub 2019 Jun 10.

Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada.

We describe Idionectes vortex gen. nov., sp. nov., a unicellular microeukaryote that swims by continuous inversion of its surface, similar to a vortex ring. This previously unreported mode of motility approximates a hypothetical concept called the 'toroidal swimmer', in which a doughnut-shaped object rotates around its circular axis and travels in the opposite direction to its outer surface motion. During swimming, the flagellum of Idionectes rotates relative to its cell body, which is normally a hallmark of prokaryotic rather than eukaryotic flagella.
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http://dx.doi.org/10.1038/s41564-019-0478-6DOI Listing
October 2019

The Relative Importance of Modeling Site Pattern Heterogeneity Versus Partition-Wise Heterotachy in Phylogenomic Inference.

Syst Biol 2019 11;68(6):1003-1019

Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, 5850 College Street, Halifax, Nova Scotia B3H 4R2, Canada.

Large taxa-rich genome-scale data sets are often necessary for resolving ancient phylogenetic relationships. But accurate phylogenetic inference requires that they are analyzed with realistic models that account for the heterogeneity in substitution patterns amongst the sites, genes and lineages. Two kinds of adjustments are frequently used: models that account for heterogeneity in amino acid frequencies at sites in proteins, and partitioned models that accommodate the heterogeneity in rates (branch lengths) among different proteins in different lineages (protein-wise heterotachy). Although partitioned and site-heterogeneous models are both widely used in isolation, their relative importance to the inference of correct phylogenies has not been carefully evaluated. We conducted several empirical analyses and a large set of simulations to compare the relative performances of partitioned models, site-heterogeneous models, and combined partitioned site heterogeneous models. In general, site-homogeneous models (partitioned or not) performed worse than site heterogeneous, except in simulations with extreme protein-wise heterotachy. Furthermore, simulations using empirically-derived realistic parameter settings showed a marked long-branch attraction (LBA) problem for analyses employing protein-wise partitioning even when the generating model included partitioning. This LBA problem results from a small sample bias compounded over many single protein alignments. In some cases, this problem was ameliorated by clustering similarly-evolving proteins together into larger partitions using the PartitionFinder method. Similar results were obtained under simulations with larger numbers of taxa or heterogeneity in simulating topologies over genes. For an empirical Microsporidia test data set, all but one tested site-heterogeneous models (with or without partitioning) obtain the correct Microsporidia+Fungi grouping, whereas site-homogenous models (with or without partitioning) did not. The single exception was the fully partitioned site-heterogeneous analysis that succumbed to the compounded small sample LBA bias. In general unless protein-wise heterotachy effects are extreme, it is more important to model site-heterogeneity than protein-wise heterotachy in phylogenomic analyses. Complete protein-wise partitioning should be avoided as it can lead to a serious LBA bias. In cases of extreme protein-wise heterotachy, approaches that cluster similarly-evolving proteins together and coupled with site-heterogeneous models work well for phylogenetic estimation.
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http://dx.doi.org/10.1093/sysbio/syz021DOI Listing
November 2019

An updated phylogeny of the reveals that the parasitic and have independent origins.

Elife 2019 02 25;8. Epub 2019 Feb 25.

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada.

The is an extraordinarily diverse and ancient group of bacteria. Previous attempts to infer its deep phylogeny have been plagued with methodological artefacts. To overcome this, we analyzed a dataset of 200 single-copy and conserved genes and employed diverse strategies to reduce compositional artefacts. Such strategies include using novel dataset-specific profile mixture models and recoding schemes, and removing sites, genes and taxa that are compositionally biased. We show that the and (both groups of intracellular parasites of eukaryotes) are not sisters to each other, but instead, the has a derived position within the . A synthesis of our results also leads to an updated proposal for the higher-level taxonomy of the . Our robust consensus phylogeny will serve as a framework for future studies that aim to place mitochondria, and novel environmental diversity, within the .
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http://dx.doi.org/10.7554/eLife.42535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447387PMC
February 2019

Nuclear genome sequence of the plastid-lacking cryptomonad Goniomonas avonlea provides insights into the evolution of secondary plastids.

BMC Biol 2018 11 28;16(1):137. Epub 2018 Nov 28.

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.

Background: The evolution of photosynthesis has been a major driver in eukaryotic diversification. Eukaryotes have acquired plastids (chloroplasts) either directly via the engulfment and integration of a photosynthetic cyanobacterium (primary endosymbiosis) or indirectly by engulfing a photosynthetic eukaryote (secondary or tertiary endosymbiosis). The timing and frequency of secondary endosymbiosis during eukaryotic evolution is currently unclear but may be resolved in part by studying cryptomonads, a group of single-celled eukaryotes comprised of both photosynthetic and non-photosynthetic species. While cryptomonads such as Guillardia theta harbor a red algal-derived plastid of secondary endosymbiotic origin, members of the sister group Goniomonadea lack plastids. Here, we present the genome of Goniomonas avonlea-the first for any goniomonad-to address whether Goniomonadea are ancestrally non-photosynthetic or whether they lost a plastid secondarily.

Results: We sequenced the nuclear and mitochondrial genomes of Goniomonas avonlea and carried out a comparative analysis of Go. avonlea, Gu. theta, and other cryptomonads. The Go. avonlea genome assembly is ~ 92 Mbp in size, with 33,470 predicted protein-coding genes. Interestingly, some metabolic pathways (e.g., fatty acid biosynthesis) predicted to occur in the plastid and periplastidal compartment of Gu. theta appear to operate in the cytoplasm of Go. avonlea, suggesting that metabolic redundancies were generated during the course of secondary plastid integration. Other cytosolic pathways found in Go. avonlea are not found in Gu. theta, suggesting secondary loss in Gu. theta and other plastid-bearing cryptomonads. Phylogenetic analyses revealed no evidence for algal endosymbiont-derived genes in the Go. avonlea genome. Phylogenomic analyses point to a specific relationship between Cryptista (to which cryptomonads belong) and Archaeplastida.

Conclusion: We found no convincing genomic or phylogenomic evidence that Go. avonlea evolved from a secondary red algal plastid-bearing ancestor, consistent with goniomonads being ancestrally non-photosynthetic eukaryotes. The Go. avonlea genome sheds light on the physiology of heterotrophic cryptomonads and serves as an important reference point for studying the metabolic "rewiring" that took place during secondary plastid integration in the ancestor of modern-day Cryptophyceae.
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http://dx.doi.org/10.1186/s12915-018-0593-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260743PMC
November 2018

Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes.

Nature 2018 12 14;564(7736):410-414. Epub 2018 Nov 14.

Department of Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Nova Scotia, Canada.

Almost all eukaryote life forms have now been placed within one of five to eight supra-kingdom-level groups using molecular phylogenetics. The 'phylum' Hemimastigophora is probably the most distinctive morphologically defined lineage that still awaits such a phylogenetic assignment. First observed in the nineteenth century, hemimastigotes are free-living predatory protists with two rows of flagella and a unique cell architecture; to our knowledge, no molecular sequence data or cultures are currently available for this group. Here we report phylogenomic analyses based on high-coverage, cultivation-independent transcriptomics that place Hemimastigophora outside of all established eukaryote supergroups. They instead comprise an independent supra-kingdom-level lineage that most likely forms a sister clade to the 'Diaphoretickes' half of eukaryote diversity (that is, the 'stramenopiles, alveolates and Rhizaria' supergroup (Sar), Archaeplastida and Cryptista, as well as other major groups). The previous ranking of Hemimastigophora as a phylum understates the evolutionary distinctiveness of this group, which has considerable importance for investigations into the deep-level evolutionary history of eukaryotic life-ranging from understanding the origins of fundamental cell systems to placing the root of the tree. We have also established the first culture of a hemimastigote (Hemimastix kukwesjijk sp. nov.), which will facilitate future genomic and cell-biological investigations into eukaryote evolution and the last eukaryotic common ancestor.
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http://dx.doi.org/10.1038/s41586-018-0708-8DOI Listing
December 2018

A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes.

Genome Biol Evol 2018 10 1;10(10):2813-2822. Epub 2018 Oct 1.

Department of Parasitology, Faculty of Science, Charles University, Vestec, Czech Republic.

Mitochondria have evolved diverse forms across eukaryotic diversity in adaptation to anoxia. Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. Transport of proteins via TIM complexes, composed of three proteins of the Tim17 protein family (Tim17/22/23), is one of the key unifying aspects of mitochondria and mitochondria-derived organelles. However, multiple experimental and bioinformatic attempts have so far failed to identify the nature of TIM in mitosomes of the anaerobic metamonad protist, Giardia intestinalis, one of the few experimental models for mitosome biology. Here, we present the identification of a single G. intestinalis Tim17 protein (GiTim17), made possible only by the implementation of a metamonad-specific hidden Markov model. While very divergent in primary sequence and in predicted membrane topology, experimental data suggest that GiTim17 is an inner membrane mitosomal protein, forming a disulphide-linked dimer. We suggest that the peculiar GiTim17 sequence reflects adaptation to the unusual, detergent resistant, inner mitosomal membrane. Specific pull-down experiments indicate interaction of GiTim17 with mitosomal Tim44, the tethering component of the import motor complex. Analysis of TIM complexes across eukaryote diversity suggests that a "single Tim" translocase is a convergent adaptation of mitosomes in anaerobic protists, with Tim22 and Tim17 (but not Tim23), providing the protein backbone.
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http://dx.doi.org/10.1093/gbe/evy215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200312PMC
October 2018

Molecular clocks provide little information to date methanogenic Archaea.

Nat Ecol Evol 2018 11;2(11):1676-1677

Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.1038/s41559-018-0687-zDOI Listing
November 2018

Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients.

Oncoimmunology 2018;7(7):e1442166. Epub 2018 Mar 13.

Department of General and Oncologic Dermatology, Ambroise-Paré hospital, APHP, & EA 4340 "Biomarkers in cancerology and hemato-oncology", UVSQ, Université Paris-Saclay, Boulogne-Billancourt, France.

Information on the role of radiotherapy in anti-PD-1 monoclonal antibody-treated melanoma patients is limited. We report on a prospective cohort of advanced melanoma patients treated simultaneously with radiotherapy and anti-PD-1 therapy between 01/01/15 and 30/06/16. Tumor evaluations (RECIST 1.1) were performed every 3 months on radiated and non-radiated lesions. Twenty-five advanced melanoma patients (64% AJCC stage IV M1c, 64% on second-line treatment or more, 60% with elevated LDH serum levels) were included. Radiotherapy was performed early (median: 24 days) after the first anti-PD-1 dose in 15 patients with rapidly progressing symptomatic lesion(s) or later (median: 5.4 months) in 10 patients with progressive disease (PD) despite PD-1 blockade. Radiotherapy was limited to one organ in 24 patients and consisted mainly of hypo-fractioned radiotherapy (median dose 26 Gy in 3-5 fractions, 17 patients) or brain radiosurgery (5 patients). Median follow-up after first anti-PD-1 dose was 16.9 m (range 2.7-27.4), with 44% of patients alive at last follow-up. For radiated lesions, rates of complete (CR), partial (PR) responses, stable disease (SD) or PD were 24%, 12%, 24%, and 32%, respectively. For non-radiated lesions, rates of CR, PR, SD, and PD were 20%, 19%, 12%, and 40%, respectively. Responses achieved after radiotherapy for radiated and non-radiated areas were correlated (Pearson correlation : 0.89, <0.0001) suggesting an abscopal effect. Five patients with CR remained disease-free after discontinuation of anti-PD-1 for a median of 9.5 months. No unusual adverse event was recorded. Hypo-fractionated radiotherapy may enhance efficacy of anti-PD1 therapy in difficult-to-treat patients. Controlled studies are needed.
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http://dx.doi.org/10.1080/2162402X.2018.1442166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053300PMC
March 2018

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors.

Ann Rheum Dis 2019 08 23;78(8):e82. Epub 2018 Jun 23.

Department of Dermatology, AP-HP Hôpital Saint Louis, Paris, France.

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http://dx.doi.org/10.1136/annrheumdis-2018-213857DOI Listing
August 2019

Combined morphological and phylogenomic re-examination of malawimonads, a critical taxon for inferring the evolutionary history of eukaryotes.

R Soc Open Sci 2018 Apr 4;5(4):171707. Epub 2018 Apr 4.

Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.

Modern syntheses of eukaryote diversity assign almost all taxa to one of three groups: Amorphea, Diaphoretickes and Excavata (comprising Discoba and Metamonada). The most glaring exception is Malawimonadidae, a group of small heterotrophic flagellates that resemble Excavata by morphology, but branch with Amorphea in most phylogenomic analyses. However, just one malawimonad, , has been studied with both morphological and molecular-phylogenetic approaches, raising the spectre of interpretation errors and phylogenetic artefacts from low taxon sampling. We report a morphological and phylogenomic study of a new deep-branching malawimonad, n. gen. n. sp. Electron microscopy revealed all canonical features of 'typical excavates', including flagellar vanes (as an opposed pair, unlike but like many metamonads) and a composite fibre. Initial phylogenomic analyses grouped malawimonads with the Amorphea-related orphan lineage , separate from a Metamonada+Discoba clade. However, support for this topology weakened when more sophisticated evolutionary models were used, and/or fast-evolving sites and long-branching taxa (FS/LB) were excluded. Analyses of '-FS/LB' datasets instead suggested a relationship between malawimonads and metamonads. The 'malawimonad+metamonad signal' in morphological and molecular data argues against a strict Metamonada+Discoba clade (i.e. the predominant concept of Excavata). A Metamonad+Discoba clade should therefore not be assumed when inferring deep-level evolutionary history in eukaryotes.
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http://dx.doi.org/10.1098/rsos.171707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936906PMC
April 2018

Microbial eukaryotes have adapted to hypoxia by horizontal acquisitions of a gene involved in rhodoquinone biosynthesis.

Elife 2018 04 26;7. Epub 2018 Apr 26.

Centre for Comparative Genomics and Evolutionary Bioinformatics (CGEB), Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada.

Under hypoxic conditions, some organisms use an electron transport chain consisting of only complex I and II (CII) to generate the proton gradient essential for ATP production. In these cases, CII functions as a fumarate reductase that accepts electrons from a low electron potential quinol, rhodoquinol (RQ). To clarify the origins of RQ-mediated fumarate reduction in eukaryotes, we investigated the origin and function of , a gene encoding an RQ biosynthetic enzyme. is very patchily distributed across eukaryotes and bacteria adapted to hypoxia. Phylogenetic analyses suggest lateral gene transfer (LGT) of from bacteria to eukaryotes occurred at least twice and the gene was transferred multiple times amongst protists. We demonstrate that RquA functions in the mitochondrion-related organelles of the anaerobic protist and is correlated with the presence of RQ. These analyses reveal the role of gene transfer in the evolutionary remodeling of mitochondria in adaptation to hypoxia.
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http://dx.doi.org/10.7554/eLife.34292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953543PMC
April 2018

Accelerated Estimation of Frequency Classes in Site-Heterogeneous Profile Mixture Models.

Mol Biol Evol 2018 05;35(5):1266-1283

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada.

As a consequence of structural and functional constraints, proteins tend to have site-specific preferences for particular amino acids. Failing to adjust for heterogeneity of frequencies over sites can lead to artifacts in phylogenetic estimation. Site-heterogeneous mixture-models have been developed to address this problem. However, due to prohibitive computational times, maximum likelihood implementations utilize fixed component frequency vectors inferred from sequences in a database that are external to the alignment under analysis. Here, we propose a composite likelihood approach to estimation of component frequencies for a mixture model that directly uses the data from the alignment of interest. In the common case that the number of taxa under study is not large, several adjustments to the default composite likelihood are shown to be necessary. In simulations, the approach is shown to provide large improvements over hierarchical clustering. For empirical data, substantial improvements in likelihoods are found over mixtures using fixed components.
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http://dx.doi.org/10.1093/molbev/msy026DOI Listing
May 2018

Demystifying Eukaryote Lateral Gene Transfer (Response to Martin 2017 DOI: 10.1002/bies.201700115).

Bioessays 2018 05 15;40(5):e1700242. Epub 2018 Mar 15.

Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, P.O. Box 15000, Halifax, CAN B3H 4R2, Nova Scotia, Canada.

In a recent BioEssays paper [W. F. Martin, BioEssays 2017, 39, 1700115], William Martin sharply criticizes evolutionary interpretations that involve lateral gene transfer (LGT) into eukaryotic genomes. Most published examples of LGTs in eukaryotes, he suggests, are in fact contaminants, ancestral genes that have been lost from other extant lineages, or the result of artefactual phylogenetic inferences. Martin argues that, except for transfers that occurred from endosymbiotic organelles, eukaryote LGT is insignificant. Here, in reviewing this field, we seek to correct some of the misconceptions presented therein with regard to the evidence for LGT in eukaryotes.
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http://dx.doi.org/10.1002/bies.201700242DOI Listing
May 2018

Reply to 'Eukaryote lateral gene transfer is Lamarckian'.

Authors:
Andrew J Roger

Nat Ecol Evol 2018 05;2(5):755

Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.1038/s41559-018-0522-6DOI Listing
May 2018

Clinical Profile of Lipid Transfer Protein Syndrome in a Mediterranean Area.

J Investig Allergol Clin Immunol 2018;28(1):58-60

Allergy Section, Hospital Universitari Germans Trias i Pujol, UAB, Badalona, Spain.

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http://dx.doi.org/10.18176/jiaci.0209DOI Listing
September 2019