62 research outputs found
Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development
Get PDFThe post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. The parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. Indeed, the number of RNA-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique RNA regulators dedicated to gene expression in these evolutionarily ancient organisms. Here, we report that a small CCCH zinc finger protein, TbZFP3, enhances development between life-cycle stages in Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both with the translational machinery and with other small CCCH proteins previously implicated in trypanosome developmental control. Antibodies to this protein also co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively expressed, it exhibits developmentally regulated association with polyribosomes, and mutational analysis demonstrates that this association is essential for the expression of phenotype. TbZFP3 is therefore a novel regulator of developmental events in kinetoplastids that acts at the level of the post-transcriptional control of gene expression
Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study
Get PDFBackground: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far.
Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.
Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)).
Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis
JAK1 (Janus kinase 1)
Get PDFReview on JAK1 (Janus kinase 1), with data on DNA, on the protein encoded, and where the gene is implicated
Mise en scène de la parole magistrale dans un cours de philosophie
No full textInternational audienceThis article comes from a doctoral thesis defended in 2018 and dedicated to the teaching of philosophy in high school. It comes within a clinical approach of psychoanalytical orientation in educational sciences. The author explores some latent aspects of the discourse held by a philosophy teacher of secondary education interviewed within a non-directive clinical interview conducted from the following instruction: "I would like you to tell me, as it comes to you, what you feel when you teach philosophy." Starting from a psychic elaboration of counter-transferential feelings in resonance with several enunciation elements of the speech of this teacher related to spectacle and staging, the author analyses unconscious psychic mechanisms that seem to underlie the evocation, by this professor, of a certain dramatisation of her teaching practice. After having highlighted the partially conscious psychic investment of which this dramatisation seems to be the object in this evocation, the author makes the hypothesis that a part of a certain professional psychic suffering which seems to underlie the discourse of this teacher could be an effect of the psychic efforts inherent in this supposed staging of the act of teaching. Indeed, if this evocation of a staging of the magistrate speech is obviously a part of the pleasure she says she takes when teaching, it also includes several metaphorizations of which a latent suffering is the central and common element, which forms, as regards the unconscious psychic field, a heuristic paradox. Through this article, it is thus about trying to better understand certain psychic effects that might provoke, on the evocation of a teaching practice, a dramatisation inflected by unconscious psychic processes.Cet article fait suite à une thèse soutenue en novembre 2018. Intitulée Enseigner la philosophie au lycée. Hypothèses cliniques d'orientation psychanalytique, cette recherche porte sur l'enseignement de la philosophie en France, tel qu'il est actuellement dispensé dans les classes terminales des séries générales et technologiques des lycées. Elle est plus particulièrement consacrée à la manière dont des professeurs de philosophie vivent l'acte d'enseigner leur discipline et elle a été construite sur l'analyse d'entretiens cliniques non-directifs réalisés auprès de six professeurs de philosophie de l'enseignement secondaire à partir de la consigne suivante : « J'aimerais que vous me disiez, comme ça vous vient, comment vous vivez le fait d'enseigner la philosophie ». Au cours de cette recherche, enseignant moi-même la philosophie au lycée, j'ai été particulièrement attentif aux ressentis dont font part des enseignants de cette discipline lorsqu'ils évoquent leur rapport au déploiement de la parole magistrale dans l'espace de la classe. Comment vivent-ils leur enseignement si celui-ci est, pour eux, étroitement lié à l'exercice d'une certaine démonstrativité déclamatoire et se heurte ordinairement à la difficulté de composer avec un groupe-classe dont l'attention peut être inégalement soutenue ? À quels processus psychiques inconscients cette composante irréductible de l'acte d'enseigner soumet-elle la parole magistrale lorsque sont interrogées, dans le cadre d'entretiens cliniques, des déclinaisons individuelles et singulières ? Après avoir précisé le cadre théorique de cette recherche, je présenterai l'un des entretiens que j'ai réalisés. Puis, à partir d'une analyse du contenu latent de certains éléments d'énonciation de cet entretien, j'exposerai quelques-unes des hypothèses auxquelles celle-ci m'a mené. Cadre épistémologique de cette recherche Ma recherche s'inscrit dans le cadre d'une clinique d'orientation psychanalytique de recherche en sciences de l'éducation. Elle porte, en-8
Mise en scène de la parole magistrale dans un cours de philosophie
No full textInternational audienceThis article comes from a doctoral thesis defended in 2018 and dedicated to the teaching of philosophy in high school. It comes within a clinical approach of psychoanalytical orientation in educational sciences. The author explores some latent aspects of the discourse held by a philosophy teacher of secondary education interviewed within a non-directive clinical interview conducted from the following instruction: "I would like you to tell me, as it comes to you, what you feel when you teach philosophy." Starting from a psychic elaboration of counter-transferential feelings in resonance with several enunciation elements of the speech of this teacher related to spectacle and staging, the author analyses unconscious psychic mechanisms that seem to underlie the evocation, by this professor, of a certain dramatisation of her teaching practice. After having highlighted the partially conscious psychic investment of which this dramatisation seems to be the object in this evocation, the author makes the hypothesis that a part of a certain professional psychic suffering which seems to underlie the discourse of this teacher could be an effect of the psychic efforts inherent in this supposed staging of the act of teaching. Indeed, if this evocation of a staging of the magistrate speech is obviously a part of the pleasure she says she takes when teaching, it also includes several metaphorizations of which a latent suffering is the central and common element, which forms, as regards the unconscious psychic field, a heuristic paradox. Through this article, it is thus about trying to better understand certain psychic effects that might provoke, on the evocation of a teaching practice, a dramatisation inflected by unconscious psychic processes.Cet article fait suite à une thèse soutenue en novembre 2018. Intitulée Enseigner la philosophie au lycée. Hypothèses cliniques d'orientation psychanalytique, cette recherche porte sur l'enseignement de la philosophie en France, tel qu'il est actuellement dispensé dans les classes terminales des séries générales et technologiques des lycées. Elle est plus particulièrement consacrée à la manière dont des professeurs de philosophie vivent l'acte d'enseigner leur discipline et elle a été construite sur l'analyse d'entretiens cliniques non-directifs réalisés auprès de six professeurs de philosophie de l'enseignement secondaire à partir de la consigne suivante : « J'aimerais que vous me disiez, comme ça vous vient, comment vous vivez le fait d'enseigner la philosophie ». Au cours de cette recherche, enseignant moi-même la philosophie au lycée, j'ai été particulièrement attentif aux ressentis dont font part des enseignants de cette discipline lorsqu'ils évoquent leur rapport au déploiement de la parole magistrale dans l'espace de la classe. Comment vivent-ils leur enseignement si celui-ci est, pour eux, étroitement lié à l'exercice d'une certaine démonstrativité déclamatoire et se heurte ordinairement à la difficulté de composer avec un groupe-classe dont l'attention peut être inégalement soutenue ? À quels processus psychiques inconscients cette composante irréductible de l'acte d'enseigner soumet-elle la parole magistrale lorsque sont interrogées, dans le cadre d'entretiens cliniques, des déclinaisons individuelles et singulières ? Après avoir précisé le cadre théorique de cette recherche, je présenterai l'un des entretiens que j'ai réalisés. Puis, à partir d'une analyse du contenu latent de certains éléments d'énonciation de cet entretien, j'exposerai quelques-unes des hypothèses auxquelles celle-ci m'a mené. Cadre épistémologique de cette recherche Ma recherche s'inscrit dans le cadre d'une clinique d'orientation psychanalytique de recherche en sciences de l'éducation. Elle porte, en-8
A new contribution to the moss flora of the Inner Seychelles
No full textAn updated list of the mosses of the Inner Seychelles is given based on the previous literature and collections of the first author in 2008. It includes data on the frequency of species as well as distributional data for the individual islands. The moss flora of the islands is characterized. Campylopus brevirameus Dixon is regarded as synonym of C. julaceus ssp. arbogastii (Renauld & Cardot) J.-P.Frahm. Brachymenium dicranoides, Bryum alpinum, Campylopus flaccidus, C. flexuosus, Ectropothecium brachycladulum, E. chenagonii and E. perrotii are reported as new to the Seychelles. Garckea flexuosa, Syrrhopodon involutus and S. prolifer are reported as new to La Digue, Bryum leptospeiron, Brachymenium exile and Calymperes afzelii as new to Praslin
A revised checklist of Hawaiian mosses
No full textA revised and updated literature-based checklist of Hawaiian mosses is presented. Geographic coverage includes the eight main Hawaiian Islands; the Northwestern Hawaiian Islands are excluded. The checklist is alphabetically ordered by scientific names; the family is noted for each genus. Synonyms and misapplied names are cross-referenced to the accepted names. A bibliography of supporting references is included
Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids.
Get PDFBACKGROUND: Different proteins are required in widely different quantities to build a living cell. In most organisms, transcription control makes a major contribution to differential expression. This is not the case in trypanosomatids where most genes are transcribed at an equivalent rate within large polycistronic clusters. Thus, trypanosomatids must use post-transcriptional control mechanisms to balance gene expression requirements. RESULTS: Here, the evidence for translational selection, the enrichment of 'favoured' codons in more highly expressed genes, is explored. A set of highly expressed, tandem-repeated genes display codon bias in Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. The tRNA complement reveals forty-five of the sixty-one possible anticodons indicating widespread use of 'wobble' tRNAs. Consistent with translational selection, cognate tRNA genes for favoured codons are over-represented. Importantly, codon usage (Codon Adaptation Index) correlates with predicted and observed expression level. In addition, relative codon bias is broadly conserved among syntenic genes from different trypanosomatids. CONCLUSION: Synonymous codon bias is correlated with tRNA gene copy number and with protein expression level in trypanosomatids. Taken together, the results suggest that translational selection is the dominant mechanism underlying the control of differential protein expression in these organisms. The findings reveal how trypanosomatids may compensate for a paucity of canonical Pol II promoters and subsequent widespread constitutive RNA polymerase II transcription
Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
Get PDFAntigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections
Crystal structure of recombinant human interleukin-22
No full textInterleukin-22 (IL-10-related T cell-derived inducible factor/IL-TIF/IL-22) is a novel cytokine belonging to the IL-10 family. Recombinant human IL-22 (hIL-22) was found to activate the signal transducers and activators of transcription factors I and 3 as well as acute phase reactants in several hepatoma cell lines, suggesting its involvement in the inflammatory response. The crystallographic structure of recombinant hIL-22 has been solved at 2.0 Angstrom resolution using the SIRAS method. Contrary to IL-10, the hIL-22 dimer does not present an interpenetration of the secondary-structure elements belonging to the two distinct polypeptide chains but results from interface interactions between monomers. Structural differences between these two cytokines, revealed by the crystallographic studies, clearly indicate that, while a homodimer of IL-10 is required for signaling, hIL-22 most probably interacts with its receptor as a monomer.1081051106
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