Search

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

EnglishBased on an empirical research on teacher training practices in Switzerland that brings together 28 training sequences on written production, this paper proposes an overview of the professional gestures that trainers develop while preparing future teachers. Six major professional gestures organize the dynamics of the observed trainer’s formation and action. Two gestures take place outside the classroom: planning and evaluating of the training work. Four gestures take place during the implementation of sequences in the teacher’s presence: conceptualizing of writing and of teaching and learning; mobilization of practices and experiences of written production at class; equipping with resources and tools for the teaching of writing; regulating of teachers’ learning and practices. This paper brings examples to illustrate the trainer’s action on the mastering of the written production. The results showed the importance of the trainer’s action to develop the necessary professional skills for the written production teaching. Keywords: Teacher training practices. Training sequences. Written production. Professional gestures. portuguesA partir de uma pesquisa empirica sobre as praticas de formacao do professorado na Suica que reune 28 sequencias de formacao sobre a producao escrita, este artigo propoe uma visao geral dos gestos profissionais que desenvolvem os formadores ao preparar os futuros docentes. Seis grandes gestos profissionais organizam a dinâmica da formacao observada e o agir do formador. Dois gestos se realizam fora das aulas: planificacao e avaliacao do trabalho de treinamento. Quatro gestos tem lugar no curso da implementacao das sequencias em presenca dos docentes: conceptualizacao da escrita e do seu ensino e aprendizagem, mobilizacao das praticas e experiencias da producao escrita na aula, equipar com recursos e ferramentas para o ensino a escrita, regulacao das aprendizagens e das praticas dos professores. O artigo ilustra com exemplos o agir do formador no dominio da producao escrita. Os resultados da pesquisa mostram a importância do agir do formador para o desenvolvimento de competencias profissionais para o ensino da producao escrita. Palavras-chave: Praticas de formacao de professores. Sequencias de treinamento. Producao escrita. Gestos profissionais.

Protein S-nitrosylation is now recognized as a ubiquitous regulatory mechanism. Like any post-translational modifications, S-nitrosylation is critical for the control of numerous cellular processes. It is now clear that S-nitrosylation is playing a double game, enhancing or inhibiting the tumor growth or the induction of cell death. Thanks to research aimed at demonstrating NO cytotoxic effects, new therapeutic strategies based on NO donor drugs have emerged. Although therapeutic NO donors can target a large number of proteins, the cellular mechanism is still not fully understood. This review reflects the current state of knowledge on S-nitrosylated proteins that take part of the oncogenic and apoptotic signaling, putting forward proteins with potential interest in cancer therapy.

Gold phosphine complexes, such as auranofin, have been recognized for decades as antirheumatic agents. Clinical trials are now underway to validate their use in anticancer or anti-HIV treatments. However, their mechanisms of action remain unclear. A challenging question is whether the gold phosphine complex is a prodrug that is administered in an inactive precursor form or rather that the gold atom remains attached to the phosphine ligand during treatment. In this study, we present two novel gold complexes, which we compared to auranofin and to their phosphonium analogue. The chosen ligand is a phosphine-based smart probe, whose strong fluorescence depends on the presence of the gold atom. The in vitro biological action of the gold complexes and the phosphonium derivative were investigated, and a preliminary in vivo study in healthy zebrafish larvae allowed us to evaluate gold complex biodistribution and toxicity. The different analyses carried out showed that these gold complexes were stable and behaved differently from phosphonium and auranofin, both in vitro and in vivo. Two-photon microscopy experiments demonstrated that the cellular targets of these gold complexes are not the same as those of the phosphonium analogue. Moreover, despite similar IC50 values in some cancer cell lines, gold complexes displayed a low toxicity in vivo, in contrast to the phosphonium salt. They are therefore suitable for future in vivo investigations.

International audience

Drug development for castration resistant prostate cancer (CRPC) is challenging, since this cancer is still associated with high mortality and limited therapeutic options. In 2004, docetaxel became the first-line chemotherapy for CRPC improving survival by a few months and remains the standard of care in CRPC patients. However, existing or developing resistance to docetaxel in patients is the main limitation of its efficacy. The present review presents the molecular mechanisms involved in docetaxel toxicity and in docetaxel resistance in prostate cancer cells. We outlined the endogenous mechanisms of resistance and the role of tumor microenvironment in the resistance of CRPC to docetaxel. This has led us to focus on molecules associated with resistance, such as the molecular chaperones heat shock proteins (HSPs) and clusterin (CLU), and the cytokines interleukin-6 (IL-6) and the divergent member of the tumor growth factor family MIC-1 (macrophage inhibitory cytokine-1 also named GDF-15). We discuss their interest as blood-based markers to monitor docetaxel resistance. Finally, new therapies intended to overcome docetaxel resistance of CRPC targeted on these molecular resistance pathways are present.

Since the communicative orientation of the 1970s in French language teaching, texts, documents and situations have been used to contextualize language learning. In this perspective, discursive genres and language functions have been established as the main language objects to be taught. In French as a first language (FFL), French is mainly studied through discursive genres, whereas in French as a (foreign or) second language (FSL), language functions are primarily used. This epistemological background shows similarities and differences between the two domains dedicated to the teaching of French. They share the same object, French, and they have a notion in common, the discursive genre. In both fields, the discursive genre is approached as a teaching/learning object, although it comes second in FSL compared to its importance in FFL. What distinguishes the approach of genre in FFL and FSL? How is genre used in FSL teaching? These are the two questions that will be discussed in this paper, based on a review of positions in FFL and FSL, and the presentation of various pedagogical uses of discursive genres in FSL., Le tournant communicatif des années 1970 a marqué l’évolution des travaux en didactique du français en orientant l’enseignement de la langue à partir de l’étude de documents et de contextes de communication variés. Dans cette perspective, les objets langagiers privilégiés sont le genre discursif et l’acte de parole. Si en didactique du français langue première (FL1), l’accès à la langue semble s’effectuer principalement par l’entremise des genres, en didactique du français langue étrangère (FLE), l’entrée privilégiée passe essentiellement par le recours aux actes de parole, sans pour autant que la notion de genre ne soit exclue des préoccupations du champ. Cet arrière-plan épistémologique laisse entrevoir l’existence de points de divergence, mais également de lieux de rencontre entre les deux contextes. Ceux-ci ont en effet en partage un même objet, le français et une même notion, le genre. Dans les deux cas, le genre est appréhendé comme objet d’enseignement-apprentissage, bien que l’importance de cette entrée demeure encore assez secondaire en didactique du FLE au regard de la place qui lui est accordée en FL1. Pour autant, où se situe la ligne de démarcation entre le genre en FL1 et le genre en FLE ? En outre, lorsqu’on opère un resserrement sur les pratiques en FLE, comment cette entrée est-elle appréhendée ? Ce sont ces deux questions qui sont abordées dans cet article à travers un état des lieux des positionnements privilégiés en FL1 et en FLE et la présentation de pistes d’exploitation des genres en FLE.

Les notions d’unite didactique en francais langue etrangere (FLE) ou de sequence didactique en francais langue maternelle ou premiere (FLM-FL1) s’inscrivent dans des histoires disciplinaires differentes mais paralleles sur le plan didactique : elles concernent toutes deux l’objet « langue francaise » et traitent de l’organisation des activites d’enseignement-apprentissage. Dans le domaine du FLE, la notion d’unite didactique vise a donner un cadre a l’organisation des activites de decouverte et d’appropriation de la langue pour des non-francophones afin de developper leur capacite a communiquer et a agir dans cette langue. Dans le domaine du FLM-FL1, la notion de sequence didactique a emerge a partir des recherches linguistiques et didactiques sur les types textuels et les genres discursifs et sur leur enseignabilite, notamment sur celle des genres discursifs propres a l’oral. L’organisation des activites d’enseignement-apprentissage en cours de francais (FLE ou FLM-FL1) se trouvant au cœur du metier d’enseignant, cela entraine des questions comme : quel enchainement d’activites est potentiellement propice a l’apprentissage de la langue ou d’un genre discursif ? Dans quelle coherence doit se construire une suite d’exercices proposes aux apprenants ? Comment un cadre d’organisation des activites peut-il etre adaptable dans differents contextes educatifs ? A partir des travaux didactiques qui presentent des schemas reperes pour l’organisation des unites ou des sequences, nous comparons les fonctions de ces deux notions modelisees afin d’en determiner les convergences et les variations en termes de planification de l’action enseignante et des contours des objets enseignes. Nous illustrons notre propos d’exemples d’unites ou de sequences, ce qui nous permet d’analyser en quoi ces modelisations proposent un cadre a la fois coherent et adaptable en situation.

Nitric oxide synthase (NOS) produces nitric oxide (NO) from arginine. Three NOS isoforms have been identified in mammals, namely a neuronal (NOS1), an inducible (NOS2) and an endothelial (NOS3) enzyme. In zebrafish genome, one nos1 gene and two nos2 genes (nos2a and nos2b) were observed. We cloned zebrafish nos2a cDNA and compared nos2a and nos2b sequences, expression and inducibility. When analyzed by reverse transcription-PCR, the expression of nos2a remained very low during initial development, then increased at 96 hpf, while nos2b was expressed from 6 hpf and subsequently remained stable. Expression of nos2a is detected in the head, eye and gut regions by WISH experiments performed at 48, 72 and 96 hpf larvae. In adults, nos2a expression varies from one tissue to another whereas nos2b is expressed in all studied tissues. Both nos2 isoforms can be induced by pro-inflammatory or mechanical stresses (tissue injury). In vitro as in vivo stimulations with Poly I:C and lipopolysaccharides (LPS) enhanced more dramatically nos2a than nos2b expression. After tail transection in 4 dpf larvae a strong increase of nos2a and nos2b expression was evidenced in the regeneration site, skin cells and for the nos2b gene in neuromasts. Phylogenetic and syntenic analyses show that nos2b gene was associated with syntenic genes identified for nos2 genes in vertebrate. This is not the case for the nos2a gene, despite zebrafish nos2a presenting the inducible property of a classical vertebrate nos2 isoform. A myristoylation consensus site was detected at the N-terminal extremity of zebrafish Nos2b, a property shared with mammal NOS3 isoforms. Thus, the evolution of nos2 genes in zebrafish provides a typical example of gene divergence after duplication.

International audience; Protein S-nitrosylation is now recognized as a ubiquitous regulatory mechanism. Like any post-translational modifications, S-nitrosylation is critical for the control of numerous cellular processes. It is now clear that S-nitrosylation is playing a double game, enhancing or inhibiting the tumor growth or the induction of cell death. Thanks to research aimed at demonstrating NO cytotoxic effects, new therapeutic strategies based on NO donor drugs have emerged. Although therapeutic NO donors can target a large number of proteins, the cellular mechanism is still not fully understood. This review reflects the current state of knowledge on S-nitrosylated proteins that take part of the oncogenic and apoptotic signaling, putting forward proteins with potential interest in cancer therapy.; La S-nitrosylation est une modification post-traductionnelle par laquelle le monoxyde d’azote (NO) régule l’activité des protéines. Cette modification particulière exerce un rôle déterminant dans le contrôle des mécanismes de transduction du signal qui gouvernent de nombreux processus cellulaires. Aujourd’hui, il apparaît que la S-nitrosylation joue un double jeu, activateur ou inhibiteur, dans la signalisation cellulaire de la croissance tumorale ou l’induction de la mort cellulaire. Grâce aux travaux démontrant l’effet cytotoxique du NO, de nouvelles stratégies thérapeutiques visant à utiliser des donneurs de NO ont été développées. Leur mode d’action, encore mal connu, cible un nombre important de protéines. Cette revue fait le point sur l’état actuel de nos connaissances sur les protéines S-nitrosylées de la signalisation oncogénique et apoptotique, en mettant en avant les protéines pour lesquelles la S-nitrosylation représente un intérêt thérapeutique pour le traitement du cancer.

Dans ce texte, nous analysons le traitement de la pratique professionnelle dans deux séquences de formation portant sur l’enseignement de la production écrite. Dans un premier temps, nous observons les caractéristiques des dispositifs de formation prévoyant l’alternance entre le terrain scolaire et l’institution de formation. La focale est ensuite mise sur les interactions entre formateur et formés à l’intérieur de deux activités de formation ciblant le retour sur la pratique. L’intérêt de cette double perspective est de mieux comprendre la circulation des savoirs d’un lieu à un autre et comment cette circulation est mise au service du développement de l’agir enseignant., In this contribution, we analyse the treatment of professional practice in two training sequences dedicated to the teaching of written French. Firstly, we examine the characteristics of the training devices organised with a combination of school field and training institution scheme. We then focus on interactions between trainer and trainees within two training activities aimed at sharing and reflecting on practicum. The interest of this double perspective lies in the understanding of knowledge circulation between school field and training institution and how this circulation serves the development of teachers’ action.

Numerous approaches have been described to identify nitric oxide (NO), a free radical involved in various physiological and pathophysiological processes. One of these approaches is based on the use of chemical probes whose transformation by NO generates highly fluorescent derivatives, permitting detection of NO down to nanomolar concentrations. Here, we show that the cell-permeant diaminofluorophore 4-amino-5-methylamino-2′-7′-difluorofluorescein diacetate (DAF-FM-DA) can be used to detect NO production sites in a living vertebrate, the zebrafish Danio rerio. The staining pattern obtained in larvae includes the bulbus arteriosus, forming bones, the notochord, and the caudal fin. The specificity of the signal was confirmed by its decrease in animals exposed to a NO scavenger or a NO synthase inhibitor and its increase in the presence of a NO donor. Using this method, NO production was observed to change along development in the notochord and the caudal fin whereas it remained stable in the bulbus arteriosus. Local changes in NO production in response to stressful conditions were also detected by this method. Altogether, labeling with DAF-FM DA is an efficient method to monitor changes in NO production in live zebrafish under physiological as well as pathophysiological conditions, suggesting applications to drug screening and molecular pharmacology.

Triterpenoid saponins, which are present in plants and some marine animals, exert various important pharmacological effects. The present study examines the effects of adianthifoliosides A, B, and D (AdA, AdB, and AdD) together with two prosapogenins (Pro1 and Pro2) obtained from Albizia adianthifolia (Mimosaceae) on human leukemia T-cells (Jurkat cells) and on splenocytes. AdA, AdB, and AdD were found to exhibit a cytotoxic effect on Jurkat cells, whereas the prosapogenins were found to exert a lymphoproliferative effect on this cell type. Furthermore, all tested compounds were found to exert a synergistic lymphoproliferative activity with concanavalin A (ConA) on splenocytes. The concentrations where the saponins were found to be cytotoxic on Jurkat cells are far below the concentration of hemolysis. These results indicate that another mechanism than membrane permeabilization formation is responsible of the cell cytotoxicity. Thus, we demonstrated that at 5 μM for AdA and at 1 μM for AdD, these compounds induce apoptosis in Jurkat cells. Early apoptotic events were detected by flow cytometry analysis by using a double annexin-V-FITC and propidium iodide staining. In addition, a disrupted mitochondrial membrane potential was observed in cells treated with AdA, AdB, and AdD. Furthermore, a DNA ladder was observed when Jurkat cells were incubated with 1 μM AdD for 24 h. By comparison between the biological activities of the native compounds with the prosapogenins, we show in this work the important role of the acylation and esterification by different moieties at C-21 and C-28 of the aglycone (acacic acid) in the apoptosis-inducing capacity. Particularly, the monoterpene-quinovosyl moiety is shown to be important for the induction of apoptosis.

Eight new acylated triterpene saponins 1–8 were isolated from the roots of Polygala arenaria as four inseparable (E)/(Z) mixtures of the 4-methoxycinnamoyl and 3,4-dimethoxycinnamoyl derivatives by repeated MPLC over silica gel. Their structures were established mainly by 600-MHz 2D-NMR techniques (1H,1H-COSY, TOCSY, NOESY, HSQC, HMBC) as 3-O-(β-D-glucopyranosyl)presenegenin 28-(O-β-D-galactopyranosyl-(14)-O-[β-D-glucopyranosyl-(13)]-O-β-D-xylopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-{4-O-[(E)-4-methoxycinnamoyl]}-β-D-fucopyranosyl) ester and its (Z)-isomer (1/2), 3-O-(β-D-glucopyranosyl)presenegenin 28-(O-β-D-galactopyranosyl-(14)-O-[β-D-glucopyranosyl-(13)]-O-β-D-xylopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-{4-O-[(E)-3,4-dimethoxycinnamoyl]}-β-D-fucopyranosyl) ester and its (Z)-isomer (3/4), 3-O-(β-D-glucopyranosyl)presenegenin 28-(O-β-D-glucopyranosyl-(13)-O-α-L-arabinopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-{4-O-[(E)-4-methoxycinnamoyl]}-β-D-fucopyranosyl) ester and its (Z)-isomer (5/6), and 3-O-(β-D-glucopyranosyl)presenegenin 28-(O-β-D-glucopyranosyl-(13)-O-α-L-arabinopyranosyl-(14)-O-α-L-rhamnopyranosyl-(12)-{4-O-[(E)-3,4-dimethoxycinnamoyl]}-β-D-fucopyranosyl) ester and its (Z)-isomer (7/8) (presenegenin=(2β,3β)-2,3,27-trihydroxyolean-12-ene-23,28-dioic acid). In our in vitro lymphocyte proliferation assay (Jurkat T-leukemia cells), a fraction containing 1–4 showed a concentration-dependent immunomodulatory effect. This effect was not found for the prosapogenin (tenuifolin=3-O-(β-D-glucopyranosyl)presenegenin), underlining the importance of the acyloligosaccharidic moiety.

The purpose of this review is to point out some important proteins targeted by chemotherapy in cancer patients as well as by NO (S-nitrosylation) in tumor cells. We, therefore, confronted data from clinical and preclinical studies and discussed their respective anti-tumor effects to determine whether the associations of chemotherapy with NO donor therapy may be considered as novel therapeutic approaches (considered as rational therapeutic interventions).

Three new acylated triterpene saponins 1-3, with a quillaic acid as aglycon, were isolated from the roots of Silene fortunei together with a known phytoecdysteroid (20-hydroxyecdysone). The compounds were characterized mainly by a combination of 2D NMR techniques, mass spectrometry, and chemical methods. Saponins 1-3, jenisseensosides C and D (4, 5), and 6 (deacylated form of 2/3 and 4/5) were found to stimulate the proliferation of the Jurkat tumor cell lines at low concentration. At high concentration, 2/3 and 4/5 inhibited the proliferation of the cells and suggested the induction of apoptosis.

The axolotl MHC is composed of multiple polymorphic class I loci linked to class II B loci. In this report, evidence of the existence of one class II B locus (Amme-DAB) that codes for two different transcripts is given. A 2.1-kb transcript is translated to a complete β chain and a shorter transcript of 1.8 kb encodes a molecule lacking the β1 domain. For two complete class II B mRNA synthesized, up to one mRNA devoid of the β1 domain is synthesized. Alternative splicing involving a peptide binding domain at a class II B locus evidenced in axolotl (Ambystoma mexicanum) is also observed for A. trigrinum, the tiger salamander. Very little variability is found among various axolotl MHC class II B cDNA sequences, and the same allele is obtained from inbred and wild axolotls. The transcription of one MHC class B locus in two class II B isoforms in thymic cells and in splenic lymphocytes may shed new light on the well-known deficient immune responder state of the axolotl.

Despite the fact that the axolotl (Ambystoma spp. a urodele amphibian) displays a large T-cell repertoire and a reasonable B-cell repertoire, its humoral immune response is slow (60 days), non-anamnestic, with a unique IgM class. The cytotoxic immune response is slow as well (21 days) with poor mixed lymphocyte reaction stimulation. Therefore, this amphibian can be considered as immunodeficient. The reason for this subdued immune response could be an altered antigenic presentation by major histocompatibility complex (MHC) molecules. This article summarizes our work on axolotl MHC genes. Class I genes have been characterized and the cDNA sequences show a good conservation of non-polymorphic peptide binding positions of the alpha chain as well as a high diversity of the variable amino acids positions, suggesting that axolotl class I molecules can present numerous antigenic epitopes. Moreover, class I genes are ubiquitously transcribed at the time of hatching. These class I genes also present an important polylocism and belong to the same linkage group as the class II B gene; they can be reasonably considered as classical class Ia genes. However, only one class II B gene has been characterized so far by Southern blot analysis. As in higher vertebrates, this gene is transcribed in lymphoid organs when they start to be functional. The sequence analysis shows that the peptide binding region of this class II beta chain is relatively well conserved, but most of all does not present any variability in the beta 1 domain in inbred as well as in wild axolotls, presuming a limited antigenic presentation of few antigenic epitopes. The immunodeficiency of the axolotl could then be explained by an altered class II presentation of antigenic peptides, putting into question the existence of cellular co-operation in this lower vertebrate. It will be interesting to analyze the situation in other urodele species and to determine whether our observations in axolotl represent a normal feature in urodele amphibians. But already two different models in amphibians, Xenopus and axolotl, must be considered in our search for understanding immune system and MHC evolution.

Nonaspanins constitute a family of proteins, also called TM9SF, characterized by a large non-cytoplasmic domain and nine putative transmembrane domains. This family is highly conserved through evolution and comprises three members in Saccharomyces cerevisiae, Dictyostelium discoideum, and Drosophila melanogaster, and four members are reported in mammals (TM9SF1–TM9SF4). Genetic studies in Dictyostelium and Drosophila have shown that TM9SF members are required for adhesion and phagocytosis in innate immune response, furthermore, human TM9SF1 plays a role in the regulation of autophagy and human TM9SF4 in tumor cannibalism. Here we report that the zebrafish genome encodes five members of this family, TM9SF1–TM9SF5, which show high level of sequence conservation with the previously reported members. Expression analysis in zebrafish showed that all members are maternally expressed and continue to be present throughout embryogenesis to adults. Gene expression could not be regulated by pathogen-associated molecular patterns such as LPS, CpG, or Poly I:C. By bioinformatic analyses of 80 TM9SF protein sequences from yeast, plants, and animals, we confirmed a very conserved protein structure. An evolutionary conserved immunoreceptor tyrosine-based inhibition motif has been detected in the cytoplasmic domain between transmembrane domain (TM) 7 and TM8 in TM9SF1, TM9SF2, TM9SF4 and TM9SF5, and at the extreme C-terminal end of TM9SF4. Finally, a conserved TRAF2 binding domain could also be predicted in the cytoplasmic regions of TM9SF2, TM9SF3, TM9SF4, and TM9SF5. This confirms the hypothesis that TM9SF proteins may play a regulatory role in a specific and ancient cellular mechanism that is involved in innate immunity.

International audience; Two new oleanane-type triterpene saponins, adianthifoliosides A (1) and B (2), were isolated from a 95% ethanolic extract of roots of Albizia adianthifolia. Their structures were elucidated mainly by using a combination of 600 MHz 1D and 2D NMR techniques (COSY, NOESY, TOCSY, HSQC, and HMBC) and by FABMS and HRESIMS. Compounds 1 and 2 were characterized as glycosides of acacic acid acylated by an o-hydroxybenzoyl unit. The crude saponin mixture (CSM), compounds 1 and 2 together with 3 and 4 (prosapogenins obtained from the mild alkaline hydrolysate of the CSM), were evaluated for immunomodulatory activity on the Jurkat T cell line and for hemolytic property against sheep erythrocytes. Compound 2 and, to a lesser extent, 1 and 3 were found to exhibit a dose-dependent immunomodulatory effect in the concentration range 10-2-10 µM, whereas 4 showed a lymphoproliferative activity in the same concentration range. Among the compounds tested, only 1 and 2 were found to be hemolytic. The genus Albizia comprises about 150 species widely distributed in the tropics, with the greatest diversity in Africa and Central and South America. 1 Albizia species have been reported to contain alkaloids, steroids, triter-penoid saponins, and flavonols. 2 Some saponins such as julibrosides J 1 , J 2 , and J 9 from Albizia julibrissin 3,4 possess various biological effects, such as inhibitory activity against the KB cancer cell line in vitro. In a previous contribution, we reported the isolation and structure determination of two prosapogenins (3 and 4) isolated from the butanol extract of the mild alkaline hydrolysate of the crude saponin fraction of the roots of Albizia adianthifolia (Schumach.) W. F. Wight (Mimo-saceae). 5 The further investigation of the saponins of this plant, obtained as a complex mixture, afforded two new acylated triterpene saponins, adianthifoliosides A (1) and B (2), from the 95% ethanolic extract of the roots of A. adianthifolia. This paper deals with the isolation and structure elucidation of these new acylated triterpene glycosides (1 and 2) and the evaluation of the immuno-modulatory activity of 1-4 (Chart 1) and the crude saponin mixture (CSM) on Jurkat T cell proliferation (human T cell leukemia) and the hemolytic activity of 1-4 on sheep erythrocytes. Results and Discussion The 95% ethanolic extract of the roots of A. adianthifolia was purified by precipitation with diethyl ether, yielding a crude saponin mixture, which was then dialyzed for 2 days. The powder obtained was submitted to column chromatography over Sephadex LH-20 and was separated by repeated medium-pressure liquid chromatography (MPLC) over normal Si gel, yielding compounds 1 and 2. Their structures were elucidated mainly by 1D and 2D NMR spectroscopy (COSY, TOCSY, NOESY, HSQC, and HMBC) and by FABMS and HRESIMS. Compound 1 was obtained as an amorphous powder. The HRESI mass spectrum (positive-ion mode) exhibited a quasimolecular ion peak at m/z 1714.7490 [M + Na] + (calcd 1714.7465), consistent with a molecular formula of C 79 H 121-NO 38. Upon acid hydrolysis with 2 N TFA at 120 °C, 1 afforded the aglycon 6, which was identified as acacic acid lactone (the 21,28-lactone derivative of acacic acid obtained under the experimental conditions used), by comparison of its NMR data with literature values. 6 The native aglycon was characterized as acacic acid from the 2D NMR spectra from 1. The sugars obtained from the saponin hydrolysate were identified as glucose, fucose, rhamnose, arabinose, and xylose by comparison with authentic samples. However , the presence of an N-acetamido group [IR 1639 and 1570 cm-1 ; 1 H NMR δ H 2.13 (3H, s, MeCO) and δ H 8.91 (1H, d, J) 8.8 Hz, NH); 13 C NMR δ C 22.9 and 171.9], together with the 1 H and 13 C NMR data of the C-2 of the Glc 1 (δ H 4.40 and δ C 56.8), suggested the presence of one 2-(acetylamino)-2-deoxyglucose (Glc 1 NAc) unit. In addition, alkaline hydrolysis of 1 afforded salicylic acid (SA, o-hydroxybenzoic acid, 7), identified by comparison of its 1 H and 13 C NMR data with those reported, 7 and a prosapoge-nin whose spectroscopic NMR data were in good agreement with those of 4. 5 The above data suggested that 1 is a 21-acyl-3,28-bisdesmoside. This was confirmed by the observation of glycosylation-and acylation-induced shifts in the 13 C NMR spectrum at δ C 88.7 (downfield shift of C-3), δ C 76.5 (downfield shift of C-21), and δ C 174.4 (upfield shift of C-28). The 1 H NMR spectrum of 1 displayed signals for seven anomeric protons at δ H 6.06 (br s), 5.83 (d, J) 7.5 Hz), 5.77 (br s), 5.10 (d, J) 7.5 Hz), 4.91 (d, J) 7.5 Hz), 4.90 (d, J) 7.8 Hz), and 4.79 (d, J) 8.0 Hz), which correlated with the carbon signals at δ C 109.8, 94.9, 101.2, 104.7, 103.8, 105.6, and 102.5, respectively, in the HSQC spectrum. Starting from the anomeric proton of each sugar unit, all the protons within each spin system were delineated using COSY with the aid of TOCSY and NOESY spectra. After assignments of the protons, the 13 C NMR resonances of each sugar unit were identified by HSQC and further confirmed by HMBC. The COSY and TOCSY spectra

Two novel triterpenoid saponins (1 and 2) have been isolated from the roots of Acanthophyllum squarrosum. The structures were established mainly by a combination of 2D NMR techniques as 3-O-beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-be ta-D-glucuronopyranosylgypsogenin-28-O-beta-D-xylopyranosyl-(1-->3 )-b eta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L- rhamnopyranosyl-(1-->3)]-beta-D-fucopyranoside (1) and 3-O-beta-D-glucopyranosylgypsogenin-28-O-alpha-L-rhamnopyranosyl-( 1-- >2)-alpha-L-arabinopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->6 )]- beta-D-glucopyranoside (2). Compound 1 showed a moderate concentration-dependent immunomodulatory effect in an in vitro lymphocyte proliferation assay.

The MHC of the urodele amphibian Ambystoma mexicanum consists of multiple polymorphic class I loci linked, so far as yet known, to a single class II B locus. This architecture is very different from that of the anuran amphibian Xenopus. The number of class I loci in the axolotl can vary from 6 to 21 according to the haplotypes as shown by cDNA analysis and Southern blot studies in families. These loci can be classified into seven sequence groups with features ranging from the class Ia to the class Ib type. All individuals express genes from at least three of the seven groups, and all individuals possess the class Ia-like type.

Class I major histocompatibility complex (Mhc) cDNA clones were isolated from axolotl mRNA by polymerase chain reaction (PCR) and by screening a cDNA phage library. The nucleotide and predicted amino acid sequences show definite similarities to the Mhc class Ialpha molecules of higher vertebrates. Most of the amino acids in the peptide binding region that dock peptides at their N and C termini in mammals are conserved. Several amino acids considered to be important for the interaction of beta2-microglobulin with the Mhc alpha chain are also conserved in the axolotl sequence. The fact that axolotl class I A cDNAs are ubiquitously expressed and highly polymorphic in the alpha1 and alpha2 domains suggests the classical nature of axolotl class I A genes.

Adrian Grimes and colleagues showed in a previous report that zebrafish bulbus arteriosus and the smooth muscle component of the chick cardiac outflow tract may be specifically labeled by DAF-2DA. Using this fluorescent dye they could distinguish the zebrafish bulbus arteriosus from "true" cardiac chambers, the atrium and ventricle (Grimes AC, Stadt HA, Shepherd IT, Kirby ML. Solving an enigma: arterial pole development in the zebrafish heart. Dev Biol 2006 Feb 15;290(2):265−76). The authors regret not including this information in the original version of their article.

One of the key features of tumor cells is the acquisition of resistance to apoptosis. Thus, novel therapeutic strategies that circumvent apoptotic resistance and result in tumor elimination are needed. One strategy to induce apoptosis is to activate death receptor signaling pathways. In the tumor microenvironment, stimulation of Fas, Death receptor 4 (DR4) and tumor necrosis factor receptor 1 (TNFR1) can initiate multiple signaling pathways driving either tumor promotion or elimination. Nitric oxide (NO) is an important signaling molecule now understood to play a dual role in cancer biology. More and more attention is directed toward the role displayed by S-nitrosylation, the incorporation of an NO moiety to a cysteine thiol group, in promoting cell death in tumor cells. Protein post-translation modification by S-nitrosylation has decisive roles in regulating signal-transduction pathways. In this review, we summarize several examples of protein modification by S-nitrosylation that regulate signaling pathways engaged by members of the TNF superfamily (Fas ligand (FasL), Tumor-necrosis-factor-related apoptosis inducing ligand (TRAIL) and TNFalpha (TNFα)) and the way it influences cell fate decisions., Graphical abstract fx1, Highlights • An overview of NO in regulating signaling pathways engaged by FasL, TRAIL and TNFα. • S-nitrosylation regulates protein activity and cancer cell death. • Exploiting NO for cancer therapy.

International audience

International audience

International audience

International audience; Louis Porcher a été un infatigable passeur de frontières, disciplinaires, institutionnelles, personnelles. Son œuvre multiforme en constitue une forme originale et elle continue de nous interroger sur le temps présent. Son action envers les enfants de migrants frappe à la fois par sa précocité et par son actualité. Son approche sociologique et philosophique « impliquée » dans son temps nous invite une nouvelle fois à franchir les frontières et à nous affranchir de tout conformisme sociologique ou historique pour aller vers les vaincus de l’histoire et les damnés de la terre (W. Benjamin)…