Viral cystatin evolution and three-dimensional structure modelling: A case of directional selection acting on a viral protein involved in a host-parasitoid interaction

<p>Abstract</p> <p>Background</p> <p>In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily.</p> <p>Results</p> <p>We show that <it>cystatins </it>are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of <it>Cotesia congregata </it>bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different <it>cystatin </it>forms which evolved under different selective constraints and are characterized by independent adaptive duplication events.</p> <p>Conclusion</p> <p>Positive selection acts to maintain <it>cystatin </it>gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence factors, as was already proposed in previous functional studies.</p

Genomic dissection of an extended phenotype:Oak galling by a cynipid gall wasp

Galls are plant tissues whose development is induced by another organism for the inducer's benefit. 30,000 arthropod species induce galls, and in most cases the inducing effectors and target plant systems are unknown. Cynipid gall wasps are a speciose monophyletic radiation that induce structurally complex galls on oaks and other plants. We used a model system comprising the gall wasp Biorhiza pallida and the oak Quercus robur to characterise inducer and host plant gene expression at defined stages through the development of galled and ungalled plant tissues, and tested alternative hypotheses for the origin and type of galling effectors and plant metabolic pathways involved. Oak gene expression patterns diverged markedly during development of galled and normal buds. Young galls showed elevated expression of oak genes similar to legume root nodule Nod factor-induced early nodulin (ENOD) genes and developmental parallels with oak buds. In contrast, mature galls showed substantially different patterns of gene expression to mature leaves. While most oak transcripts could be functionally annotated, many gall wasp transcripts of interest were novel. We found no evidence in the gall wasp for involvement of third-party symbionts in gall induction, for effector delivery using virus-like-particles, or for gallwasp expression of genes coding for plant hormones. Many differentially and highly expressed genes in young larvae encoded secretory peptides, which we hypothesise are effector proteins exported to plant tissues. Specifically, we propose that host arabinogalactan proteins and gall wasp chitinases interact in young galls to generate a somatic embryogenesis-like process in oak tissues surrounding the gall wasp larvae. Gall wasp larvae also expressed genes encoding multiple plant cell wall degrading enzymes (PCWDEs). These have functional orthologues in other gall inducing cynipids but not in figitid parasitoid sister groups, suggesting that they may be evolutionary innovations associated with cynipid gall induction

The initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort

In chronic myeloid leukemia, the identification of early molecular predictors of stable treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation is challenging. The predictive values of residual disease (BCR::ABL1 quantification) at months 3 and 6 and more recently, BCR::ABL1 transcript halving time (HT) have been described, but no study compared the predictive value of different early parameters. Using a real-world cohort of 408 patients, we compared the performance of the ELTS score, BCR::ABL1 HT, and residual disease at month 3 and 6 to predict the molecular response, achievement of the TKI discontinuation criteria, and TFR maintenance. The performances of BCR::ABL1 HT and residual disease at month 3 were similar. Residual disease at month 6 displayed the best performance for predicting the optimal response (area under the ROC curve between 0.81 and 0.92; cut-off values: 0.11% for MR4 at month 24 and 0.12% for MR4.5 at month 48). Conversely, no early parameter predicted reaching the TKI discontinuation criteria and TFR maintenance. We obtained similar results when patients were divided in subgroups by first-line treatment (imatinib vs second generation TKI, 2G-TKI). We identified a relationship between ELTS score, earlier milestones and TFR maintenance only in the 2G-TKI group. In conclusion, this first comparative study of early therapeutic response parameters showed that they are excellent indicators of TKI efficacy (BCR::ABL1 transcript reduction) and best responders. Conversely, they did not predict the achievement of the TKI discontinuation criteria and TFR maintenance, suggesting that other parameters are involved in TFR maintenance

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Sexualidade e câncer de mama: uma revisão sistemática da literatura

O objetivo deste estudo foi compreender como o câncer de mama e seus tratamentos afetam a vivência da sexualidade da mulher acometida. Foi realizada uma revisão sistemática qualitativa de artigos científicos, publicados entre 2000 e 2010, disponíveis nas bases de dados PubMed, Web of Science, LILACS e SciELO. Foram obtidos 50 artigos cujos textos foram categorizados segundo análise de conteúdo temática. Foram identificadas seis categorias temáticas: a cirurgia mamária e os demais tratamentos para o câncer de mama; a experiência da mulher acometida; o relacionamento afetivo-sexual; estudos sobre relação entre sexualidade e características específicas do câncer; os profissionais de saúde e a atenção à sexualidade; e propostas para amenizar as consequências negativas dos tratamentos na sexualidade. Há necessidade de novos estudos a respeito dos aspectos culturais da sexualidade, diversidade sexual, relacionamento com o parceiro, formação do profissional de saúde e intervenções em sexualidade no contexto do câncer de mama

Death and the Societies of Late Antiquity

Ce volume bilingue, comprenant un ensemble de 28 contributions disponibles en français et en anglais (dans leur version longue ou abrégée), propose d’établir un état des lieux des réflexions, recherches et études conduites sur le fait funéraire à l’époque tardo-antique au sein des provinces de l’Empire romain et sur leurs régions limitrophes, afin d’ouvrir de nouvelles perspectives sur ses évolutions possibles. Au cours des trois dernières décennies, les transformations considérables des méthodologies déployées sur le terrain et en laboratoire ont permis un renouveau des questionnements sur les populations et les pratiques funéraires de l’Antiquité tardive, période marquée par de multiples changements politiques, sociaux, démographiques et culturels. L’apparition de ce qui a été initialement désigné comme une « Anthropologie de terrain », qui fut le début de la démarche archéothanatologique, puis le récent développement d’approches collaboratives entre des domaines scientifiques divers (archéothanatologie, biochimie et géochimie, génétique, histoire, épigraphie par exemple) ont été décisives pour le renouvellement des problématiques d’étude : révision d’anciens concepts comme apparition d’axes d’analyse inédits. Les recherches rassemblées dans cet ouvrage sont articulées autour de quatre grands thèmes : l’évolution des pratiques funéraires dans le temps, l’identité sociale dans la mort, les ensembles funéraires en transformation (organisation et topographie) et les territoires de l’empire (du cœur aux marges). Ces études proposent un réexamen et une révision des données, tant anthropologiques qu’archéologiques ou historiques sur l’Antiquité tardive, et révèlent, à cet égard, une mosaïque de paysages politiques, sociaux et culturels singulièrement riches et complexes. Elles accroissent nos connaissances sur le traitement des défunts, l’emplacement des aires funéraires ou encore la structure des sépultures, en révélant une diversité de pratiques, et permettent au final de relancer la réflexion sur la manière dont les sociétés tardo-antiques envisagent la mort et sur les éléments permettant d’identifier et de définir la diversité des groupes qui les composent. Elles démontrent ce faisant que nous pouvons véritablement appréhender les structures culturelles et sociales des communautés anciennes et leurs potentielles transformations, à partir de l’étude des pratiques funéraires.This bilingual volume proposes to draw up an assessment of the recent research conducted on funerary behavior during Late Antiquity in the provinces of the Roman Empire and on their borders, in order to open new perspectives on its possible developments. The considerable transformations of the methodologies have raised the need for a renewal of the questions on the funerary practices during Late Antiquity, a period marked by multiple political, social, demographic and cultural changes. The emergence field anthropology, which was the beginning of archaeothanatology, and then the recent development of collaborative approaches between various scientific fields (archaeothanatology, biochemistry and geochemistry, genetics, history, epigraphy, for example), have been decisive. The research collected in this book is structured around four main themes: Evolution of funerary practices over time; Social identity through death; Changing burial grounds (organisation and topography); Territories of the Empire (from the heart to the margins). These studies propose a review and a revision of the data, both anthropological and archaeological or historical on Late Antiquity, and reveal a mosaic of political, social, and cultural landscapes singularly rich and complex. In doing so, they demonstrate that we can truly understand the cultural and social structures of ancient communities and their potential transformations, based on the study of funerary practices

A genomically tractable and ecologically relevant model herbivore for a model plant: new insights into the mechanisms of insect–plant interactions and evolution

International audienceThe availability of model microbial pathogens and plants has been key to characterizing resistance and virulence pathways and to shedding light on the mechanisms of host–parasite interactions and co-evolution (e.g. Allen et al. 2004, Science 306, 1957–1960; Bergelson et al. 2001, Science 292, 2281–2285). However, the absence of genetically tractable arthropod parasites of model plants has impeded so far our ability to gain better insights into the mechanisms, evolution and ecological consequences of plant–herbivore interactions. In this issue of Molecular Ecology, Whiteman et al. (2011) highlight fascinating features of a drosophilid fly, Scaptomyza flava, that feeds on the model plant Arabidopsis thaliana. They explore the potential of this system for studying insect–plant interactions with a clever mix of phenotypic and genetic experiments providing a comprehensive and persuasive argument for the validity of this model system. This study sets the ground for key developments in the unravelling of mechanisms involved in (i) plant–insect interactions and co-evolution, and (ii) transition to herbivory in arthropods and evolution of endophagous lifestyles

Evolution and Origin of Polydnavirus Virulence Genes. In Symbionts and Pathogens

International audiencePolydnaviruses (PDVs) have a unique life-cycle, comprised of a mutualistic lifestyle with their associated parasitoid wasps and a parasitic interaction with the lepidopteran wasp hosts. They are present as proviruses in the parasitoid wasps that harbor them. The female wasps produce particles that contain circular double-stranded DNA versions of the viruses that are injected into the wasps' lepidopteran hosts. This 'injected circular form' is replication deficient but is absolutely essential for the physiological regulation of caterpillars that leads to parasitoid survival. PDVs are divided into two genera, bracoviruses (BVs) and ichnoviruses (IVs) associated with tens of thousands of endoparasitoid braconid and ichneumonid wasps, respectively, belonging to the Ichneumonoidea superfamily. The absence of PDVs in basal lineages of Ichneumonoidea strongly suggests that the association of BVs with braconids and IVs with ichneumonids arose independently. In ichneumonids, PDVs have been identified in the Campopleginae and Banchinae subfamily. The unique genomic features of the first banchine virus examined to date also suggest they could have an origin distinct from those of IVs and BVs (Lapointe et al., 2007). The absence of genes involved in virus production in the injected circular form is likely to be a signature of the reductive evolution that these PDVs have been subjected to, due to their reliance on wasps for transmission and the absence of replication in host larvae. In this chapter, we will focus on the PDV circular genomes that are injected into the lepidopteran hosts and highlight how selection pressures are likely to have modeled their content, organization, gene function, and efficiency. These PDV genomes are atypical for viruses in the sense that they harbor numerous genes, many of whic

Génome et facteurs de virulence d'un polydnavirus d'hyménoptère parasitoïde

The hymenoptera Cotesia congregata lays its eggs into its host, a caterpillar of the lepidoptera Manduca sexta and introduces bracovirus (CcBV) particles. The proteins encoded by viral genes expressed in the parasitized host play an essential role for succesful parasitism, leading to modifications of host physiology such as alteration of immunity and prewandering developmental arrest. The introduction of this thesis summarizes up-to-date knowledge about insect immunity and bracoviral genes potentially involved in host physiology control. Sequencing and genome analyses demonstrated that the CcBV genome is composed of 30 double-stranded DNA circles coding for 9 multigenic families comprising protein tyrosine phosphatases, cystatins and ankyrin motif containing proteins. The characterisation of the viral genes expressed in the host is a key step toward further identification of the role of each protein in host physiology alteration. Field inversion gel electrophoresis (FIGE) allowed to physically localize PTP genes on the viral genome. Their expression was analysed on different host tissues by a multiplex RT PCR method. Next, biochemical activity tests of 2 PTPs were performed. Globally, genes of the described families are expressed in the parasitized host and some proteins have the biochemical function predicted by their conserved domains, suggesting these proteins play a role in the host physiological modifications induces by parasitism.L'hyménoptère Cotesia congregata pond dans un hôte, la chenille du lépidoptère Manduca sexta et introduit des particules virales de bracovirus (CcBV). Les protéines codées par les gènes viraux exprimées dans l'hôte parasité jouent un rôle indispensable à la réussite parasitaire, entraînant des modifications de la physiologie de l'hôte, notamment une altération de l'immunité et un arrêt du développement au stade pré-pupal. Une synthèse des connaissances actuelles sur l'immunité des insectes et les gènes de bracovirus potentiellement impliqués dans le contro le de la physiologie des hôtes est présentée en introduction. Le séquençage et l'analyse du génome de CcBV ont montré que ce génome est composé de 30 cercles d'ADN double-brin porteurs de 9 familles multigéniques : la famille des protéines tyrosines phosphatases (PTP), des cystatines, des protéines ankyrines... La caractérisation des gènes viraux exprimés dans l'hôte est une étape indispensable vers l'identification du rôle individuel de chaque protéine dans le contrôle de la physiologie de l'hôte. La technique d'électrophorèse en champs inversés (FIGE) a permis la localisation physique sur l'ensemble du génome viral des gènes de PTP. Leur expression a été analysée dans différents tissus de l'hôte parasité par une méthode de PCR multiplex. Puis des tests d'activité biochimique de 2 PTP ont été menés. Les gènes des familles décrites sont exprimés dans l'hôte parasité et certaines protéines possèdent la fonction biochimique prédite par les domaines conservés, suggérant que ces protéines jouent un rôle dans la modification de la physiologie de l'hôte induite par le parasitisme.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF