Biased V beta usage in immature thymocytes is independent of DJ beta proximity and pT alpha pairing.

During thymus development, the TCR beta locus rearranges before the TCR alpha locus. Pairing of productively rearranged TCR beta-chains with an invariant pT alpha chain leads to the formation of a pre-TCR and subsequent expansion of immature pre-T cells. Essentially nothing is known about the TCR V beta repertoire in pre-T cells before or after the expression of a pre-TCR. Using intracellular staining, we show here that the TCR V beta repertoire is significantly biased at the earliest developmental stage in which VDJ beta rearrangement has occurred. Moreover (and in contrast to the V(H) repertoire in immature B cells), V beta repertoire biases in immature T cells do not reflect proximity of V beta gene segments to the DJ beta cluster, nor do they depend upon preferential V beta pairing with the pT alpha chain. We conclude that V gene repertoires in developing T and B cells are controlled by partially distinct mechanisms.

Serum-Mediane von Placentaprotein-Markern: Relevanz der Unterschiede zwischen spontanen und nach-in-vitro-Fertilisation eingetretenen Schwangerschaften für das fetale Trisomie-Screening.

Trisomy-21 (Down syndrome) is the most frequent chromosomal abnorm- ality but only one third of cases would be detected by amniocentesis based on maternal age alone. Serum screening tests in the early second trimester increase the detec- tion rate to 60-65%, and more recently it was found that such screening was also possible in the first trimester by quantifying a diffe- rent panel of markers. The concen- trations of these placental proteins are strongly dependent on gestatio- nal age; thus control medians must be established and precise dating is essential. Serum chorionic gonado- trophin (HCG) levels were recently found to be increased in IVF preg- nancies compared to spontaneous gestations, leading to a falsely ele- vated trisomy screening risk. The aim of this preliminary study was to find out whether, in the first-trime- ster screening, the markers similarly differed between IVF and spontane- ous pregnancies which would call for the establishment of separate normal medians for IVF patients. We compared 24 pregnancies ob- tained after ovarian stimulation and IVF with six women after thawed embryo transfer (unstimulated cycle) and 63 gestation- and maternal-age matched spontaneously pregnant controls. A single serum was ob- tained between 6 and 16 weeks of gestation and various placental protein levels determined by im- munometric assays. Serum levels of pregnancy-associated plasma protein A (PAPP-A), which is the major marker in the first-trimes- ter screening test, were reduced in IVF pregnancies: after 9 weeks of gestation, multiples of median (MoMs) ranged between 0.23 and 3.58 (logarithmic mean 0.743). For the frozen/thawed transfers, this value was 1.08. In the 9-12 week group containing 6 cases of IVF, three thawed transfers and 25 con- trols, PAPP-A was significantly redu- ced in the stimulated compared to the nonstimulated cycles. In the late first and early second trimester the difference was not significant in our small group but the trend persisted. Pregnancies after IVF will thus show an increased incidence of false positive results in fetal trisomy-21 screening, and special medians should be established for these pati- ents.

Peripheral T-cell lymphoma with t(6;14)(p25;q11.2) translocation presenting with massive splenomegaly.

Recurrent chromosomal translocations associated to peripheral T-cell lymphomas (PTCL) are rare. Here, we report a case of PTCL, not otherwise specified (NOS) with the karyotype 46,Y,add(X)(p22),t(6;14)(p25;q11) and FISH-proved breakpoints in the IRF4 and TCRAD loci, leading to juxtaposition of both genes. A 64-year-old male patient presented with mild cytopenias and massive splenomegaly. Splenectomy showed diffuse red pulp involvement by a pleomorphic medium- to large-cell T-cell lymphoma with a CD2+ CD3+ CD5- CD7- CD4+ CD8+/- CD30- TCRbeta-F1+ immunophenotype, an activated cytotoxic profile, and strong MUM1 expression. The clinical course was marked by disease progression in the bone marrow under treatment and death at 4 months. In contrast with two t(6;14)(p25;q11.2)-positive lymphomas previously reported to be cytotoxic PTCL, NOS with bone marrow and skin involvement, this case was manifested by massive splenomegaly, expanding the clinical spectrum of PTCLs harboring t(6;14)(p25;q11.2) and supporting consideration of this translocation as a marker of biological aggressiveness.

Let-7a Is a Direct EWS-FLI-1 Target Implicated in Ewing's Sarcoma Development.

Ewing's sarcoma family tumors (ESFT) are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA) expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC) and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

The Trypanosoma cruzi Genome Project: Nuclear Karyotype and Gene Mapping of Clone CL Brener

By using improved pulsed field gel electrophoresis conditions, the molecular karyotype of the reference clone CL Brener selected for Trypanosoma cruzi genome project was established. A total of 20 uniform chromosomal bands ranging in size from 0.45 to 3.5 Megabase pairs (Mbp) were resolved in a single run. The weighted sum of the chromosomal bands was approximately 87 Mbp. Chromoblots were hybridized with 39 different homologous probes, 13 of which identified single chromosomes. Several markers showed linkage and four different linkage groups were identified, each comprising two markers. Densitometric analysis suggests that most of the chromosomal bands contain two or more chromosomes representing either homologous chromosomes and/or heterologous chromosomes with similar sizes

Proceedings of the Schistosome Genome Project

"The host-parasite relationship" is a vast and diverse research field which, despite huge human and financial input over many years, remains largely shrouded in mystery. Clearly, the adaptation of parasites to their different host species, and to the different environmental stresses that they represent, depends on interactions with, and responses to, various molecules of host and/or parasite origin. The schistosome genome project is a primary strategy to reach the goal; this systematic research project has successfully developed novel technologies for qualitative and quantitative characterization of schistosome genes and genome organization by extensive international collaboration between top quality laboratories. Schistosomes are a family of parasitic blood flukes (Phylum Platyhelminthes), which have seven pairs of autosomal chromosomes and one pair of sex chromosomes (ZZ for a male worm and ZW for a female), of a haploid genome size of 2.7x108 base pairs (Simpson et al. 1982). Schistosomes are ideal model organisms for the development of genome mapping strategies since they have a small genome size comparable to that of well-characterized model organisms such as Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), and contain functional genes with a high level of homology to the host mammalian genes. Here we summarize the current progress in the schistosome genome project, the information of 3,047 transcribed genes (Expressed Sequence Tags; EST), complete sets of cDNA and genomic DNA libraries (including YAC and cosmid libraries) with a mapping technique to the well defined schistosome chromosomes. The schistosome genome project will further identify and characterize the key molecules that are responsible for host-parasite adaptation, i.e., successful growth, development, maturation and reproduction of the parasite within its host in the near future

Towards the Physical Map of the Trypanosoma cruzi Nuclear Genome: Construction of YAC and BAC Libraries of the Reference Clone T. cruzi CL-Brener

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantages of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2,770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas disease

Genes and Chromosomes of Leishmania infantum

During recent years, several Leishmania infantum genes have been cloned and characterized. Here, we have summarized the available information on the gene organization and expression in this protozoan parasite. From a comparative analysis, the following outstanding features were found to be common to most of the genes characterized: tandemly organized genes with conserved coding regions and divergent untranslated regions, polycistronic transcription and post-transcriptional regulation of gene expression. The analysis of chromosomes of L. infantum by pulsed-field electrophoresis showed the existence of both size and number polymorphisms such that each strain has a distinctive molecular karyotype. Despite this variability, highly conserved physical linkage groups exists among different strains of L. infantum and even among Old World Leishmania species. Gene mapping on the L. infantum molecular karyotype evidenced a bias in chromosomal distribution of, at least, the evolutionary conserved genes

Importance of influx and efflux systems and xenobiotic metabolizing enzymes in intratumoral disposition of anticancer agents.

In this review, intratumoral drug disposition will be integrated into the wide range of resistance mechanisms to anticancer agents with particular emphasis on targeted protein kinase inhibitors. Six rules will be established: 1. There is a high variability of extracellular/intracellular drug level ratios; 2. There are three main systems involved in intratumoral drug disposition that are composed of SLC, ABC and XME enzymes; 3. There is a synergistic interplay between these three systems; 4. In cancer subclones, there is a strong genomic instability that leads to a highly variable expression of SLC, ABC or XME enzymes; 5. Tumor-expressed metabolizing enzymes play a role in tumor-specific ADME and cell survival and 6. These three systems are involved in the appearance of resistance (transient event) or in the resistance itself. In addition, this article will investigate whether the overexpression of some ABC and XME systems in cancer cells is just a random consequence of DNA/chromosomal instability, hypo- or hypermethylation and microRNA deregulation, or a more organized modification induced by transposable elements. Experiments will also have to establish if these tumor-expressed enzymes participate in cell metabolism or in tumor-specific ADME or if they are only markers of clonal evolution and genomic deregulation. Eventually, the review will underline that the fate of anticancer agents in cancer cells should be more thoroughly investigated from drug discovery to clinical studies. Indeed, inhibition of tumor expressed metabolizing enzymes could strongly increase drug disposition, specifically in the target cells resulting in more efficient therapies.

Physiology and transcriptome of the polycyclic aromatic hydrocarbon-degrading Sphingomonas sp. LH128 after long-term starvation.

The survival, physiology and gene expression profile of the phenanthrene-degrading Sphingomonas sp. LH128 was examined after an extended period of complete nutrient starvation and compared with a non-starved population that had been harvested in exponential phase. After 6 months of starvation in an isotonic solution, only 5 % of the initial population formed culturable cells. Microscopic observation of GFP fluorescent cells, however, suggested that a larger fraction of cells (up to 80 %) were still alive and apparently had entered a viable but non-culturable (VBNC) state. The strain displayed several cellular and genetic adaptive strategies to survive long-term starvation. Flow cytometry, microscopic observation and fatty acid methyl ester (FAME) analysis showed a reduction in cell size, a change in cell shape and an increase in the degree of membrane fatty acid saturation. Transcriptome analysis showed decreased expression of genes involved in ribosomal protein biosynthesis, chromosomal replication, cell division and aromatic catabolism, increased expression of genes involved in regulation of gene expression and efflux systems, genetic translocations, and degradation of rRNA and fatty acids. Those phenotypic and transcriptomic changes were not observed after 4 h of starvation. Despite the starvation situation, the polycyclic aromatic hydrocarbon (PAH) catabolic activity was immediate upon exposure to phenanthrene. We conclude that a large fraction of cells maintain viability after an extended period of starvation apparently due to tuning the expression of a wide variety of cellular processes. Due to these survival attributes, bacteria of the genus Sphingomonas, like strain LH128, could be considered as suitable targets for use in remediation of nutrient-poor PAH-contaminated environments.

Genomics of "chlamydia"-related bacteria

AbstractThe Chlamydiales order is an important bacterial phylum that comprises some of the most successful human pathogens such as Chlamydia trachomatis, the leading infectious cause of blindness worldwide. Since some years, several new bacteria related to Chlamydia have been discovered in clinical or environmental samples and might represent emerging pathogens. The genome sequencing of classical Chlamydia has brought invaluable information on these obligate intracellular bacteria otherwise difficult to study due to the lack of tools to perform basic genetic manipulation. The recent emergence of high-throughput sequencing technologies yielding millions of reads in a short time lowered the costs of genome sequencing and thus represented a unique opportunity to study Chlamydia-re\ated bacteria. Based on the sequencing and the analysis of Chlamydiales genomes, this thesis provides significant insights into the genetic determinants of the intracellular lifestyle, the pathogenicity, the metabolism and the evolution of Chlamydia-related bacteria. A first approach showed the efficacy of rapid sequencing coupled to proteomics to identify immunogenic proteins. This method, particularly useful for an emerging pathogen such as Parachlamydia acanthamoebae, enabled us to discover good candidates for the development of diagnostic tools that would permit to evaluate at larger scale the role of this bacterium in disease. Second, the complete genome of Waddlia chondrophila, a potential agent of miscarriage, encodes numerous virulence factors to manipulate its host cell and resist to environmental stresses. The reconstruction of metabolic pathways showed that the bacterium possesses extensive capabilities compared to related organisms. However, it is still incapable of synthesizing some essential components and thus has to import them from its host. Third, the genome comparison of Protochlamydia naegleriophila to its closest known relative Protochlamydia amoebophila revealed a particular evolutionary dynamic with the occurrence of an unexpected genome rearrangement. Fourth, a phylogenetic analysis of P. acanthamoebae and Legionella drancourtii identified several genes probably exchanged by horizontal gene transfer with other intracellular bacteria that might occur within their amoebal host. These genes often encode mechanisms for resistance to metal or toxic compounds. As a whole, the analysis of the different genomes enabled us to highlight a large diversity in size, GC percentage, repeat content as well as plasmid organization. The abundant genomic data obtained during this thesis have a wide impact since they provide the necessary bases for detailed investigations on countless aspects of the biology and the evolution of Chlamydia-related bacteria, whether in wet lab or by bioinformatical analyses.RésuméL'ordre des Chlamydiales est un important phylum bactérien qui comprend de nombreuses espèces pathogènes pour l'homme et les animaux, dont Chlamydia trachomatis, responsable du trachome, la cause majeure de cécité d'origine infectieuse à travers le monde. Durant ces dernières décennies, de nombreuses bactéries apparentées aux Chlamydia ont été découvertes dans des échantillons environnementaux ou cliniques mais leur éventuel rôle pathogène dans le développement de maladies reste peu connu. Ces bactéries sont des intracellulaires obligatoires car elles ont besoin d'une cellule hôte pour se multiplier, ce qui rend leur étude particulièrement difficile. Le développement de nouvelles technologies permettant de séquencer le génome d'un organisme rapidement et à moindre coût ainsi que l'essor des méthodes d'analyse s'y rapportant représentent une opportunité exceptionnelle d'étudier ces organismes. Dans ce contexte, cette thèse démontre l'utilité de la génomique pour développer de nouveaux outils diagnostiques ainsi que pour étudier le métabolisme de ces bactéries, leurs facteurs de virulence et leur évolution.Ainsi, une première approche a illustré l'utilité d'un séquençage rapide pour obtenir les informations nécessaires à l'identification de protéines qui sont reconnues par des anticorps humains ou animaux. Cette méthode, particulièrement utile pour un pathogène émergent tel que Parachlamydia acanthamoebae, a permis de découvrir de bons candidats pour le développement d'un outil diagnostique qui permettrait d'évaluer à plus large échelle le rôle de cette bactérie notamment dans la pneumonie. L'analyse du contenu génique de Waddlia chondrophila, un autre germe qui pourrait être impliqué dans les avortements et tes fausses-couches, a en outre mis en évidence la présence de nombreux facteurs connus qui lui permettent de manipuler son hôte. Cette bactérie possède de plus grandes capacités métaboliques que les autres Chlamydia, mais elle est incapable de synthétiser certains composants et doit donc les importer de son hôte pour subvenir à ses besoins. La comparaison du génome de Protochlamydia naegleriophila à son plus proche parent, Protochlamydia amoebophila, a dévoilé une évolution dynamique particulière avec l'occurrence d'un réarrangement majeur inattendu après la séparation de ces deux espèces. En outre, ces études ont montré l'occurrence de plusieurs transferts de gène avec d'autres organismes plus éloignés, notamment d'autres intracellulaires d'amibes, souvent pour l'acquisition de mécanismes de résistances à des composés toxiques. Les données génomiques acquises durant ce travail posent les fondements nécessaires a de nombreuses analyses qui permettront progressivement de mieux comprendre de nombreux aspects de ces bactéries fascinantes.

Mycoplasma hominis in mid-trimester amniotic fluid : relation to pregnangy outcome

RESUME Introduction : Les naissances prématurées compliquent 6-10 % des grossesses dans les pays industrialisés et contribuent de façon notable aux taux de mortalité périnatale et de morbidité néonatale. Il a été démontré que la colonisation bactérienne du liquide amniotique joue un rôle dans l'étiologie des accouchements prématurés spontanés et des ruptures prématurées des membranes. Le but de ce travail était d'évaluer la présence de Mycoplasma hominis dans le liquide amniotique prélevé au 2eme trimestre de grossesse chez des patientes asymptomatiques et de déterminer son association avec une issue défavorable de la grossesse. Matériels et méthodes : Les échantillons de liquide amniotique de 456 patientes ayant subi une amniocentèse trans-abdominale entre les 15eme et I7eme semaines de grossesse pour diverses indications ont été testés par PCR (Polymerase Chain Reaction) afin d'identifier Mycoplasma hominis. Les produits ainsi amplifiés étaient ensuite détectés par ELISA (Enzyme-Linked Immunosorbent Assay). Les données cliniques étaient obtenues après l'accouchement. Résultats : Mycoplasma hominis a été identifié dans 29 (6,4%) des échantillons de liquide amniotique. Le taux de menace d'accouchement prématuré chez les patientes positives pour Mycoplasma hominis (14,3%) était plus élevé que chez les patientes négatives (3,3 %) (p=0,01). De même, les naissances prématurées spontanées avec membranes intactes étaient plus fréquentes chez les patientes positives (10,7%) que chez les patientes négatives (1,9 %) (p=0,02). Le taux de menace d'accouchement prématuré lors d'une grossesse antérieure était plus de trois fois plus élevé chez les patientes positives, cependant ce résultat n'était pas statistiquement significatif. Finalement, la présence du mycoplasme n'était pas corrélée à la gestose, au retard de croissance intra-utérin ou aux anomalies chromosomiques foetales. Conclusions : Les résultats montrent que la présence de Mycoplasma hominis dans le liquide amniotique prélevé entre les 15eme et I7eme semaines d' aménorrhée chez des patientes asymptomatiques est associée à un taux plus élevé de menace d'accouchement prématuré et de naissances prématurées spontanées. La détection de ce microorganisme au 2eme trimestre de la grossesse peut donc identifier les patientes à risque de menace d'accouchement et de naissance prématurées. Abstract Objective: The relationship between detection of Mycoplasma hominis in mid-trimester amniotic fluid and subsequent pregnancy outcome was investigated. Study design: Amniotic fluids from 456 women of European background who underwent a transabdominal amniocentesis at weeks 15-17 of pregnancy were tested for M. hominis by polymerase chain reaction (PCR). The amplicons were hybridized to an internal probe and detected by ELISA. Pregnancy outcomes and clinical data were subsequently obtained. Results: M. hominis were identified in 29 (6.4%) of the amniotic fluids. The rate of preterm labor in women positive for M. hominis (14.3%) was higher than in the negative women (3.3%) (p = 0.01). Similarly, a spontaneous preterm birth with intact membranes occurred in 10.7% of the M. hominis-posltive women as opposed to only 1.9% of the negative women (p = 0.02). The presence of this mycoplasma was not correlated with fetal chromosomal aberrations, intrauterine growth restriction or preeclampsia. Conclusions: Detection of M. hominis in second-trimester amniotic fluids can identify women at increased risk for subsequent preterm labor and delivery.

Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release.

BACKGROUND: Bariatric surgery markedly improves glucose homeostasis in patients with type 2 diabetes even before any significant weight loss is achieved. Procedures that involve bypassing the proximal small bowel, such as Roux-en-Y gastric bypass (RYGBP), are more efficient than gastric restriction procedures such as gastric banding (GB). OBJECTIVE: To evaluate the effects of RYGBP and GB on postprandial glucose kinetics and gastro-intestinal hormone secretion after an oral glucose load. METHODS AND PROCEDURES: This study was a cross-sectional comparison among non-diabetic, weight-stable women who had undergone RYGBP (n = 8) between 9 and 48 months earlier or GB (n = 6) from 25 to 85 months earlier, and weight- and age-matched control subjects (n = 8). The women were studied over 4 h following ingestion of an oral glucose load. Total glucose and meal glucose kinetics were assessed using glucose tracers and plasma insulin, and gut hormone concentrations were simultaneously monitored. RESULTS: Patients who had undergone RYGBP showed a a more rapid appearance of exogenous glucose in the systemic circulation and a shorter duration of postprandial hyperglycemia than patients who had undergone GB and C. The response in RYGBP patients was characterized by early and accentuated insulin response, enhanced postprandial levels of glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY), and greater postprandial suppression of ghrelin. DISCUSSION: These findings indicate that RYGBP is associated with alterations in glucose kinetics and glucoregulatory hormone secretion. These alterations are probably secondary to the anatomic rearrangement of the foregut, given the fact that they are not observed after GB. Increased PYY and GLP-1 concentrations and enhanced ghrelin suppression are compatible with reduced food intake after RYGBP.

Molecular Epidemiologic Typing Systems of Bacterial Pathogens: Current Issues and Perpectives

The epidemiologic typing of bacterial pathogens can be applied to answer a number of different questions: in case of outbreak, what is the extent and mode of transmission of epidemic clone(s )? In case of long-term surveillance, what is the prevalence over time and the geographic spread of epidemic and endemic clones in the population? A number of molecular typing methods can be used to classify bacteria based on genomic diversity into groups of closely-related isolates (presumed to arise from a common ancestor in the same chain of transmission) and divergent, epidemiologically-unrelated isolates (arising from independent sources of infection). Ribotyping, IS-RFLP fingerprinting, macrorestriction analysis of chromosomal DNA and PCR-fingerprinting using arbitrary sequence or repeat element primers are useful methods for outbreak investigations and regional surveillance. Library typing systems based on multilocus sequence-based analysis and strain-specific probe hybridization schemes are in development for the international surveillance of major pathogens like Mycobacterium tuberculosis. Accurate epidemiological interpretation of data obtained with molecular typing systems still requires additional research on the evolution rate of polymorphic loci in bacterial pathogens.

Histoarchitecture of schistosomal granuloma development and involution: morphogenetic and biomechanical approaches

The authors present morphogenetic and biomechanical approaches on the concept of the Schistosoma mansoni granulomas, considering them as organoid structures that depend on cellular adhesion and sorting, forming rearrangement into hierarchical concentric layers, creating tension-dependent structures, aiming to acquire round form, since this is the minimal energy form, in which opposing forces pull in equally from all directions and are in balance. From the morphogenetic point of view, the granulomas function as little organs, presenting maturative and involutional stages in their development with final disappearance (pre-granulomatous stages, subdivided in: weakly and/or initial reactive and exudative; granulomatous stages: exudative-productive, productive and involutional). A model for the development of granulomas was suggested, according to the following stages: encapsulating, focal histolysis, fiber production, orientation and compacting and involution and desintegration. The authors concluded that schistosomal granuloma is not a tangled web of individual cells and fibers, but an organized structure composed by host and parasite components, which is not formed to attack the miracidia, but functions as an hybrid interface between two different phylogenetic beings.