Surface Texturization of Breast Implants Impacts Extracellular Matrix and Inflammatory Gene Expression in Asymptomatic Capsules:

Background: Texturing processes have been designed to improve biocompatibility and mechanical anchoring of breast implants. However, a high degree of texturing has been associated with severe abnormalities. In this study, the authors aimed to determine whether implant surface topography could also affect physiology of asymptomatic capsules. Methods: The authors collected topographic measurements from 17 different breast implant devices by interferometry and radiographic microtomography. Morphologic structures were analyzed statistically to obtain a robust breast implant surface classification. The authors obtained three topographic categories of textured implants (i.e., “peak and valleys,” “open cavities,” and “semiopened cavities”) based on the cross-sectional aspects. The authors simultaneously collected 31 Baker grade I capsules, sorted them according to the new classification, established their molecular profile, and examined the tissue organization. Results: Each of the categories showed distinct expression patterns of genes associated with the extracellular matrix (Timp and Mmp members) and inflammatory response (Saa1, Tnsf11, and Il8), despite originating from healthy capsules. In addition, slight variations were observed in the organization of capsular tissues at the histologic level. Conclusions: The authors combined a novel surface implant classification system and gene profiling analysis to show that implant surface topography is a bioactive cue that can trigger gene expression changes in surrounding tissue, even in Baker grade I capsules. The authors’ new classification system avoids confusion regarding the word “texture,” and could be transposed to implant ranges of every manufacturer. This new classification could prove useful in studies on potential links between specific texturizations and the incidence of certain breast-implant associated complications

Dynamic adaptation of mesenchymal stem cell physiology upon exposure to surface micropatterns

Human mesenchymal stem (hMSCs) are defined as multi-potent colony-forming cells expressing a specific subset of plasma membrane markers when grown on flat tissue culture polystyrene. However, as soon as hMSCs are used for transplantation, they are exposed to a 3D environment, which can strongly impact cell physiology and influence proliferation, differentiation and metabolism. Strategies to control in vivo hMSC behavior, for instance in stem cell transplantation or cancer treatment, are skewed by the un-physiological flatness of the standard well plates. Even though it is common knowledge that cells behave differently in vitro compared to in vivo, only little is known about the underlying adaptation processes. Here, we used micrometer-scale defined surface topographies as a model to describe the phenotype of hMSCs during this adaptation to their new environment. We used well established techniques to compare hMSCs cultured on flat and topographically enhanced polystyreneand observed dramatically changed cell morphologies accompanied by shrinkage of cytoplasm and nucleus, a decreased overall cellular metabolism, and slower cell cycle progression resulting in a lower proliferation rate in cells exposed to surface topographies. We hypothesized that this reduction in proliferation rate effects their sensitivity to certain cancer drugs, which was confirmed by higher survival rate of hMSCs cultured on topographies exposed to paclitaxel. Thus, micro-topographies can be used as a model system to mimic the natural cell micro-environment, and be a powerful tool to optimize cell treatment in vitro

Caractérisation d'une nouvelle famille de protéines impliquées dans l'assemblage du fuseau mitotique des plantes supérieures

Dans les cellules eucaryotes, la division cellulaire nécessite l'assemblage d'une structure bipolaire complexe appelée fuseau mitotique. L'assemblage de ce fuseau est initié par la nucléation de microtubules. Dans les cellules méiotiques de vertébrés, les microtubules sont nucléés autour de la chromatine et forment un fuseau en l'absence de centrosome. Cette voie de signalisation dépendante de la chromatine fait intervenir un gradient de Ran GTPase activée (Ran-GTP). Un des effecteurs protéiques impliqués dans cette voie est TPX2 (pour Targeting Protein for Xklp2). En interphase, TPX2 est localisée dans le noyau sous une forme inactive, associée aux importines. En début de mitose, TPX2 est libérée des importines par Ran-GTP et induit la nucléation de microtubules autour de la chromatine. Outre son importance dans la nucléation des microtubules, elle est nécessaire à la localisation de la kinase Aurora A aux pôles fusoriaux et à son activation par autophoshorylation. Une fois activée, la kinase va phosphoryler TPX2 et de nombreux autres facteurs impliqués dans différents aspects de la division cellulaire. Les plantes supérieures assemblent leur fuseau en l'absence de centrosome. Un pré-fuseau prophasique est formé avant rupture de l'enveloppe nucléaire par convergence de microtubules nucléés au niveau de la membrane externe. Des études récentes suggèrent que les mécanismes impliqués dans la formation de ce fuseau pourraient faire intervenir des voies de signalisation proches de celles rencontrées dans les cellules méiotiques animales. En effet, de nombreux gènes impliqués dans la formation du fuseau animal ont des homologues chez les plantes, codant notamment pour des kinases de type AURORA ainsi que pour Ran et ses principaux partenaires. Au cours de mon travail de thèse, j ai cherché à identifier et caractériser l'homologue végétal de TPX2 et à évaluer son implication dans l'assemblage du fuseau mitotique des plantes. Des recherches par comparaison de séquences ont permis d'identifier une protéine d'Arabidopsis encodée par un gène unique (AT1G03780), baptisée AtTPX2. Les données présentées dans cette thèse décrivent les caractéristiques structurales et fonctionnelles d'AtTPX2 et démontrent que cette protéine est l'orthologue des TPX2 animales. La dynamique particulière d'AtTPX2 qui précède la rupture de l'enveloppe nucléaire suggère que les plantes ont développé un système d'export de la protéine afin d'assembler correctement leur fuseau mitotique en l'absence de centrosome. D autre part, cette étude a permis d'identifier d'autres protéines végétales possédant certains domaines.Higher plant cells are characterized by dispersed microtubule organizing centers. During interphase, they were identified at the nuclear surface, close to the cortex and along pre-existing microtubules. However, the mechanisms of spindle microtubule assembly remain largely unknown. In acentrosomal animal cells like Xenopus oocytes, the Targeting Protein for Xklp2 (TPX2) was characterized as an essential player in perichromosomal spindle assembly, suggesting that it may be a central regulator of spindle formation without centrosomes. The aim of this work was first to identify and then to functionally characterize the Arabidopsis orthologue of TPX2. The best candidate corresponded to a single gene refered as AT1G03780. Stable transformants of Arabidopsis plants and tobacco BY-2 cells expressing GFP-AtTPX2 fusions were obtained. The fusion protein was targeted within the nucleus in interphase and actively exported shortly before nuclear envelope breakdown (NEB), probably participating in prospindle formation around the prophase nucleus. This behaviour differs from animal cells in which TPX2 nucleates microtubules only after NEB. In prometaphase, AtTPX2 colocalizes with spindle fibers and is rapidly degraded in telophase, like in vertebrates, suggesting that the protein is involved in early steps of mitosis. We characterized two nuclear localization signals, one nuclear export signal and two microtubule binding domains specific for the Arabidopsis protein, arguing in favor of its intracellular targeting and dynamics we followed. Furthermore, AtTPX2 was shown to rescue microtubule nucleation in a TPX2-depleted Xenopus extract, indicating that this function is conserved in the plant protein. In addition, the injection of anti-TPX2 antibodies in Tradescantia stamen hair cells inhibited cell division just before NEB. We identified by BLAST analysis several other proteins sharing similarities with AtTPX2 domains. Subcellular analysis has shown that these AtTPX2 like proteins have the property to bind microtubules and to shuttle between nucleoplasm and cytoplasm. All together, our data provide new insights into plant cell division, suggesting that throughout evolution, TPX2 has conserved essential functions in spindle assembly. Furthermore, this work revealed that a large number of AtTPX2 paralog does exist, suggesting a wide plant specific evolutionary radiation

ACHE, Jean-Baptiste (1905-1983). Professeur d'Histoire de la construction (1950-1979)

Pieuchot Laurent. ACHE, Jean-Baptiste (1905-1983). Professeur d'Histoire de la construction (1950-1979). In: Les professeurs du Conservatoire National des Arts et Métiers. Dictionnaire biographique 1794-1955. Tome 1 : A - K. Paris : Institut national de recherche pédagogique, 1994. pp. 74-82. (Histoire biographique de l'enseignement, 19

ACHE, Jean-Baptiste (1905-1983). Professeur d'Histoire de la construction (1950-1979)

Pieuchot Laurent. ACHE, Jean-Baptiste (1905-1983). Professeur d'Histoire de la construction (1950-1979). In: Les professeurs du Conservatoire National des Arts et Métiers. Dictionnaire biographique 1794-1955. Tome 1 : A - K. Paris : Institut national de recherche pédagogique, 1994. pp. 74-82. (Histoire biographique de l'enseignement, 19

Caractérisation d'une nouvelle famille de protéines impliquées dans l'assemblage du fuseau mitotique des plantes supérieures

Dans les cellules eucaryotes, la division cellulaire nécessite l'assemblage d'une structure bipolaire complexe appelée fuseau mitotique. L'assemblage de ce fuseau est initié par la nucléation de microtubules. Dans les cellules méiotiques de vertébrés, lesHigher plant cells are characterized by dispersed microtubule organizing centers. During interphase, they were identified at the nuclear surface, close to the cortex and along pre-existing microtubules. However, the mechanisms of spindle microtubule asse

Artificial import substrates reveal an omnivorous peroxisomal importomer

The peroxisome matrix protein importomer has the remarkable ability to transport oligomeric protein substrates across the bilayer. However, the selectivity and relation between import and overall peroxisome homeostasis remain unclear. Here, we microinject artificial import substrates and employ quantitative microscopy to probe limits and capabilities of the importomer. DNA and polysaccharides are "piggyback" imported when noncovalently bound by a peroxisome targeting signal (PTS)-bearing protein. A dimerization domain that can be tuned to systematically vary the binding dissociation constant (Kd ) shows that a Kd in the millimolar range is sufficient to promote piggyback import. Microinjection of import substrate at high levels results in peroxisome growth and a proportional accumulation of peroxisome membrane proteins (PMPs). However, corresponding PMP mRNAs do not accumulate, suggesting that this response is posttranscriptionally regulated. Together, our data show that the importomer can tolerate diverse macromolecular species. Coupling between matrix import and membrane biogenesis suggests that matrix protein expression levels can be sufficient to regulate peroxisome size

Cellular subcompartments through cytoplasmic streaming

This year, the IS2M annual meetings will focus on microfluidics. During these two days, scientists from the EUCOR network – the European campus, will present their latest findings in this field. This conference aims to provide a forum for EUCOR scientists, and more generally for scientists concern by microfluidics or any related research. The scientific committee of these meeting is thus composed by scientists from the EUCOR network (Uni Basel, Karlsruher Institut für Technologie , UNISTRA and UHA). Additionally to the EUCOR speakers, three keynote speakers from Germany, Swiss and France will be specially invited for this event

Caractérisation dʼune nouvelle famille de protéines impliquées dans lʼassemblage du fuseau mitotique des plantes supérieures

Dans les cellules eucaryotes, la division cellulaire nécessite l’assemblage d’une structure bipolaire complexe appelée fuseau mitotique. L’assemblage de ce fuseau est initié par la nucléation de microtubules. Dans les cellules méiotiques de vertébrés, les microtubules sont nucléés autour de la chromatine et forment un fuseau en l'absence de centrosome. Cette voie de signalisation dépendante de la chromatine fait intervenir un gradient de Ran GTPase activée (Ran-GTP). Un des effecteurs protéiques impliqués dans cette voie est TPX2 (pour Targeting Protein for Xklp2). En interphase, TPX2 est localisée dans le noyau sous une forme inactive, associée aux importines. En début de mitose, TPX2 est libérée des importines par Ran-GTP et induit la nucléation de microtubules autour de la chromatine. Outre son importance dans la nucléation des microtubules, elle est nécessaire à la localisation de la kinase Aurora A aux pôles fusoriaux et à son activation par autophoshorylation. Une fois activée, la kinase va phosphoryler TPX2 et de nombreux autres facteurs impliqués dans différents aspects de la division cellulaire. Les plantes supérieures assemblent leur fuseau en l'absence de centrosome. Un pré-fuseau prophasique est formé avant rupture de l'enveloppe nucléaire par convergence de microtubules nucléés au niveau de la membrane externe. Des études récentes suggèrent que les mécanismes impliqués dans la formation de ce fuseau pourraient faire intervenir des voies de signalisation proches de celles rencontrées dans les cellules méiotiques animales. En effet, de nombreux gènes impliqués dans la formation du fuseau animal ont des homologues chez les plantes, codant notamment pour des kinases de type AURORA ainsi que pour Ran et ses principaux partenaires. Au cours de mon travail de thèse, j’ai cherché à identifier et caractériser l’homologue végétal de TPX2 et à évaluer son implication dans l’assemblage du fuseau mitotique des plantes. Des recherches par comparaison de séquences ont permis d’identifier une protéine d’Arabidopsis encodée par un gène unique (AT1G03780), baptisée AtTPX2. Les données présentées dans cette thèse décrivent les caractéristiques structurales et fonctionnelles d’AtTPX2 et démontrent que cette protéine est l’orthologue des TPX2 animales. La dynamique particulière d’AtTPX2 qui précède la rupture de l’enveloppe nucléaire suggère que les plantes ont développé un système d’export de la protéine afin d’assembler correctement leur fuseau mitotique en l'absence de centrosome. D’autre part, cette étude a permis d’identifier d’autres protéines végétales possédant certains domaines.Higher plant cells are characterized by dispersed microtubule organizing centers. During interphase, they were identified at the nuclear surface, close to the cortex and along pre-existing microtubules. However, the mechanisms of spindle microtubule assembly remain largely unknown. In acentrosomal animal cells like Xenopus oocytes, the Targeting Protein for Xklp2 (TPX2) was characterized as an essential player in perichromosomal spindle assembly, suggesting that it may be a central regulator of spindle formation without centrosomes. The aim of this work was first to identify and then to functionally characterize the Arabidopsis orthologue of TPX2. The best candidate corresponded to a single gene refered as AT1G03780. Stable transformants of Arabidopsis plants and tobacco BY-2 cells expressing GFP-AtTPX2 fusions were obtained. The fusion protein was targeted within the nucleus in interphase and actively exported shortly before nuclear envelope breakdown (NEB), probably participating in prospindle formation around the prophase nucleus. This behaviour differs from animal cells in which TPX2 nucleates microtubules only after NEB. In prometaphase, AtTPX2 colocalizes with spindle fibers and is rapidly degraded in telophase, like in vertebrates, suggesting that the protein is involved in early steps of mitosis. We characterized two nuclear localization signals, one nuclear export signal and two microtubule binding domains specific for the Arabidopsis protein, arguing in favor of its intracellular targeting and dynamics we followed. Furthermore, AtTPX2 was shown to rescue microtubule nucleation in a TPX2-depleted Xenopus extract, indicating that this function is conserved in the plant protein. In addition, the injection of anti-TPX2 antibodies in Tradescantia stamen hair cells inhibited cell division just before NEB. We identified by BLAST analysis several other proteins sharing similarities with AtTPX2 domains. Subcellular analysis has shown that these AtTPX2 like proteins have the property to bind microtubules and to shuttle between nucleoplasm and cytoplasm. All together, our data provide new insights into plant cell division, suggesting that throughout evolution, TPX2 has conserved essential functions in spindle assembly. Furthermore, this work revealed that a large number of AtTPX2 paralog does exist, suggesting a wide plant specific evolutionary radiation