70 research outputs found
In situ CCVD synthesis of carbon nanotubes within a commercial ceramic foam
Consolidated nanocomposite foams containing a large quantity of carbon nanotubes (CNTs) within millimetre-sized pores are prepared for the first time. A commercial ceramic foam is impregnated by a 60 g L21 slurry of a (Mg(12x)(Co0.75Mo0.25)xO solid solution (x = 0.01, 0.05, 0.1 and 0.2) powder in ethanol. Three successive impregnations led to deposits several tens of mm thick, with a good coverage of the commercial-ceramic pore walls but without closing the pores. The materials were submitted to a CCVD treatment in H2âCH4 atmosphere in order to synthesise the CNTs. When using attrition-milled powders, the carbon is mostly in the form of nanofibres or disordered carbon rather than CNTs. Using non-milled powders produces a less-compact deposit
of catalytic material with a higher adherence to the walls of the ceramic foam. After CCVD, the carbon is mostly in the form of high-quality CNTs, as when using powder beds, their quantity being 2.5 times higher. The so-obtained consolidated nanocomposite materials show a multi-scale pore structuration
Analyses of extreme swell events on La RĂ©union Island from microseismic noise
International audienceOcean wave activity excites seismic waves that propagate through the solid earth, known as microseisms, which, once recorded on oceanic islands, can be used to analyze the swell. Here, we analyze the microseismic noise recorded in different period ranges by the permanent seismic station RER on La RĂ©union Island and by a temporary network of ten broad-band seismic stations deployed on the island to analyze extreme swell events. We perform a comparative analysis of cyclonic and austral swell events by analyzing the primary (PM, ⌠10 to 20 s period) and secondary (SM, ⌠3 to 10 s) microseisms, but also the long period secondary microseisms (LPSM, ⌠7 to 10 s), which may result from the interaction between incident ocean waves and the reflected waves off the coast. We compare the microseismic observations with buoy data when available and with predictions from numerical ocean wave models. We show that each cyclone is characterized by its own individual signature in the SM, which depends on its distance and intensity, but also on its dynamics and trajectory. Thus, the SM contains relevant information for cyclone detection and monitoring. Analyzing the PM and the LPSM, and comparing it to direct buoy observations and/or swell numerical models allows characterizing the local impact of the swell with the island in terms of amplitude, period, and sometimes, direction of propagation, making possible to use a seismic station as an ocean wave gauge. The microseisms, which link the atmosphere, the ocean and the solid Earth, can thus provide valuable observations on extreme swells, in addition to oceanic and meteorological data
Internalisation cellulaire et activité biologique de PNA bloqueurs stériques de la traduction, conjugués au peptide (R/W)9
Les Peptide Nucleic Acids (PNA) sont des oligonuclĂ©otides antisens analogues de l ADN, dont le squelette phosphodiester a Ă©tĂ© remplacĂ© par un squelette pseudo-peptidique d unitĂ©s 2-aminoĂ©thylglycine, sur lequel sont greffĂ©es des bases azotĂ©es. Des PNA dirigĂ©s contre les ARN messagers peuvent inhiber la traduction in vitro et dans les cellules humaines. Lorsqu ils sont dirigĂ©s contre la partie codante du transcrit, des PNA polypyrimidiques peuvent bloquer physiquement l Ă©longation de la traduction en stoppant la machinerie ribosomale. Le transcrit n est pas dĂ©gradĂ© et une protĂ©ine tronquĂ©e est gĂ©nĂ©rĂ©e in vitro. Dans le cas de protĂ©ines dont la surexpression conduit Ă des pathologies, des protĂ©ines tronquĂ©es inactives peuvent jouer un rĂŽle de dominant nĂ©gatif dans les cellules. Des protĂ©ines tronquĂ©es de l Insulin-like Growth Factor-1 (IGF1R), rĂ©cepteur cellulaire surexprimĂ© dans de nombreux cancers, inhibent la tumorigĂ©nĂšse et la rĂ©sistance Ă l apoptose de cellules cancĂ©reuses. La pĂ©nĂ©tration cellulaire des PNA est la principale limite Ă leur utilisation in vivo et il est nĂ©cessaire de dĂ©velopper des transporteurs efficaces pour ces oligonuclĂ©otides neutres. Les Cell Penetrating Peptides (CPP) sont des peptides naturels ou synthĂ©tiques, qui peuvent ĂȘtre conjuguĂ©s Ă diffĂ©rentes molĂ©cules pour promouvoir leur internalisation cellulaire. Les objectifs de ce travail de thĂšse Ă©taient de comprendre les critĂšres requis pour l arrĂȘt de l Ă©longation de la traduction par les PNA et d Ă©tudier leur internalisation cellulaire mĂ©diĂ©e par le CPP (R/W)9. Nous avons montrĂ© qu un couplage covalent entre ce peptide et deux PNA 13-mer permet l internalisation des conjuguĂ©s dans un systĂšme cellulaire rapporteur, conduisant Ă leur activitĂ© biologique en prĂ©sence d un agent lysosomotropique. Les conjuguĂ©s interagissent avec les glycosaminoglycanes membranaires et sont internalisĂ©s par endocytose en moins d une heure. De plus, les conjuguĂ©s formĂ©s avec un peptide analogue comportant des lysines sont six fois moins internalisĂ©s, mettant en Ă©vidence l importance des rĂ©sidus arginines du peptide (R/W)9 pour l interaction avec la membrane. Enfin, nous avons montrĂ© que le peptide (R/W)9 couplĂ© Ă un PNA dirigĂ© contre la sĂ©quence codante de l IGF1R permet son internalisation dans les cellules de cancer de la prostate et que le conjuguĂ© inhibe spĂ©cifiquement l expression de la chaĂźne b du rĂ©cepteur.Peptide nucleic acids (PNAs) are nucleic acid analogues in which the sugar-phosphate backbone has been replaced by a synthetic peptide backbone, usually comprised of N-(2-aminoethyl)-glycan units. PNAs targeted against mRNA can inhibit translation both in vitro and in human cells. Pyrimidine rich PNAs can physically block translation elongation at targets in the coding region of messenger RNA, giving rise to a truncated protein. Truncated proteins that lack a functional domain and can at the same time inhibit the function of the wild type protein are referred to as dominant negative. Truncated form of Insulin-like Growth Factor-1 receptor (IGF1R), protein overexpressed in numerous cancers, inhibits tumorigenesis and resistance to apoptosis of cancerous cells. One of the biggest limitations to the use of PNAs in vivo is their poor internalization. It is therefore necessary to develop efficient transporters able to enhance the cellular uptake of PNAs. Cell-penetrating peptides (CPPs) are natural or synthetic peptides that can be conjugated to different molecules in order to facilitate their cellular uptake. The objectives of this thesis were to understand the conditions required for the translation elongation arrest by PNAs and to study their cellular internalization mediated by CPP (R/W)9. We have shown that covalent coupling of two 13-mer PNAs to (R/W)9 facilitates their internalization in a reporter cell line, leading to their biological activity in the presence of a lysosomotropic agent such as chloroquine. The conjugates interact with membrane glycosaminoglycans and are internalized by endocytosis in less than one hour. Moreover, conjugates formed with an analogue peptide containing lysines in the place of arginines of (R/W)9 showed to be six time less efficiently internalized, suggesting the importance of arginine residues for the interaction of the conjugate with the membrane. We have also showed that the PNA targeted to the coding region of IGF1R coupled to (R/W)9 is efficiently internalized to prostate cancer cells where it inhibits the expression of the beta chain of the receptor.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. Ă©lectronique (751069903) / SudocSudocFranceF
Nanocomposite polymÚre-clusters inorganiques pour la photonique intégrée : guides rubans et nanostructures-1D
National audienc
(Eta6-arene) ruthenium(II) complexes and metallo-papain hybrid as Lewis acid catalysts of Diels-Alder reaction in water.
International audienceCovalent embedding of a (eta(6)-arene) ruthenium(II) complex into the protein papain gives rise to a metalloenzyme displaying a catalytic efficiency for a Lewis acid-mediated catalysed Diels-Alder reaction enhanced by two orders of magnitude in water
A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing
Purpose
Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the âClinVar low-hanging fruitâ reanalysis, reasons for the failure of previous analyses, and lessons learned.
Methods
Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted.
Results
We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency).
Conclusion
The âClinVar low-hanging fruitâ analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
Cellular internalization and biological activity of steric blocker PNA of translation, conjugated to the (R/W)9 peptide
Les Peptide Nucleic Acids (PNA) sont des oligonuclĂ©otides antisens analogues de lâADN, dont le squelette phosphodiester a Ă©tĂ© remplacĂ© par un squelette pseudo-peptidique dâunitĂ©s 2-aminoĂ©thylglycine, sur lequel sont greffĂ©es des bases azotĂ©es. Des PNA dirigĂ©s contre les ARN messagers peuvent inhiber la traduction in vitro et dans les cellules humaines. Lorsquâils sont dirigĂ©s contre la partie codante du transcrit, des PNA polypyrimidiques peuvent bloquer physiquement lâĂ©longation de la traduction en stoppant la machinerie ribosomale. Le transcrit nâest pas dĂ©gradĂ© et une protĂ©ine tronquĂ©e est gĂ©nĂ©rĂ©e in vitro. Dans le cas de protĂ©ines dont la surexpression conduit Ă des pathologies, des protĂ©ines tronquĂ©es inactives peuvent jouer un rĂŽle de dominant nĂ©gatif dans les cellules. Des protĂ©ines tronquĂ©es de lâInsulin-like Growth Factor-1 (IGF1R), rĂ©cepteur cellulaire surexprimĂ© dans de nombreux cancers, inhibent la tumorigĂ©nĂšse et la rĂ©sistance Ă lâapoptose de cellules cancĂ©reuses. La pĂ©nĂ©tration cellulaire des PNA est la principale limite Ă leur utilisation in vivo et il est nĂ©cessaire de dĂ©velopper des transporteurs efficaces pour ces oligonuclĂ©otides neutres. Les Cell Penetrating Peptides (CPP) sont des peptides naturels ou synthĂ©tiques, qui peuvent ĂȘtre conjuguĂ©s Ă diffĂ©rentes molĂ©cules pour promouvoir leur internalisation cellulaire. Les objectifs de ce travail de thĂšse Ă©taient de comprendre les critĂšres requis pour lâarrĂȘt de lâĂ©longation de la traduction par les PNA et dâĂ©tudier leur internalisation cellulaire mĂ©diĂ©e par le CPP (R/W)9. Nous avons montrĂ© quâun couplage covalent entre ce peptide et deux PNA 13-mer permet lâinternalisation des conjuguĂ©s dans un systĂšme cellulaire rapporteur, conduisant Ă leur activitĂ© biologique en prĂ©sence dâun agent lysosomotropique. Les conjuguĂ©s interagissent avec les glycosaminoglycanes membranaires et sont internalisĂ©s par endocytose en moins dâune heure. De plus, les conjuguĂ©s formĂ©s avec un peptide analogue comportant des lysines sont six fois moins internalisĂ©s, mettant en Ă©vidence lâimportance des rĂ©sidus arginines du peptide (R/W)9 pour lâinteraction avec la membrane. Enfin, nous avons montrĂ© que le peptide (R/W)9 couplĂ© Ă un PNA dirigĂ© contre la sĂ©quence codante de lâIGF1R permet son internalisation dans les cellules de cancer de la prostate et que le conjuguĂ© inhibe spĂ©cifiquement lâexpression de la chaĂźne ÎČ du rĂ©cepteur.Peptide nucleic acids (PNAs) are nucleic acid analogues in which the sugar-phosphate backbone has been replaced by a synthetic peptide backbone, usually comprised of N-(2-aminoethyl)-glycan units. PNAs targeted against mRNA can inhibit translation both in vitro and in human cells. Pyrimidine rich PNAs can physically block translation elongation at targets in the coding region of messenger RNA, giving rise to a truncated protein. Truncated proteins that lack a functional domain and can at the same time inhibit the function of the wild type protein are referred to as dominant negative. Truncated form of Insulin-like Growth Factor-1 receptor (IGF1R), protein overexpressed in numerous cancers, inhibits tumorigenesis and resistance to apoptosis of cancerous cells. One of the biggest limitations to the use of PNAs in vivo is their poor internalization. It is therefore necessary to develop efficient transporters able to enhance the cellular uptake of PNAs. Cell-penetrating peptides (CPPs) are natural or synthetic peptides that can be conjugated to different molecules in order to facilitate their cellular uptake. The objectives of this thesis were to understand the conditions required for the translation elongation arrest by PNAs and to study their cellular internalization mediated by CPP (R/W)9. We have shown that covalent coupling of two 13-mer PNAs to (R/W)9 facilitates their internalization in a reporter cell line, leading to their biological activity in the presence of a lysosomotropic agent such as chloroquine. The conjugates interact with membrane glycosaminoglycans and are internalized by endocytosis in less than one hour. Moreover, conjugates formed with an analogue peptide containing lysines in the place of arginines of (R/W)9 showed to be six time less efficiently internalized, suggesting the importance of arginine residues for the interaction of the conjugate with the membrane. We have also showed that the PNA targeted to the coding region of IGF1R coupled to (R/W)9 is efficiently internalized to prostate cancer cells where it inhibits the expression of the beta chain of the receptor
Internalisation cellulaire et activité biologique de PNA bloqueurs stériques de la traduction, conjugués au peptide (R/W)9
Peptide nucleic acids (PNAs) are nucleic acid analogues in which the sugar-phosphate backbone has been replaced by a synthetic peptide backbone, usually comprised of N-(2-aminoethyl)-glycan units. PNAs targeted against mRNA can inhibit translation both in vitro and in human cells. Pyrimidine rich PNAs can physically block translation elongation at targets in the coding region of messenger RNA, giving rise to a truncated protein. Truncated proteins that lack a functional domain and can at the same time inhibit the function of the wild type protein are referred to as dominant negative. Truncated form of Insulin-like Growth Factor-1 receptor (IGF1R), protein overexpressed in numerous cancers, inhibits tumorigenesis and resistance to apoptosis of cancerous cells. One of the biggest limitations to the use of PNAs in vivo is their poor internalization. It is therefore necessary to develop efficient transporters able to enhance the cellular uptake of PNAs. Cell-penetrating peptides (CPPs) are natural or synthetic peptides that can be conjugated to different molecules in order to facilitate their cellular uptake. The objectives of this thesis were to understand the conditions required for the translation elongation arrest by PNAs and to study their cellular internalization mediated by CPP (R/W)9. We have shown that covalent coupling of two 13-mer PNAs to (R/W)9 facilitates their internalization in a reporter cell line, leading to their biological activity in the presence of a lysosomotropic agent such as chloroquine. The conjugates interact with membrane glycosaminoglycans and are internalized by endocytosis in less than one hour. Moreover, conjugates formed with an analogue peptide containing lysines in the place of arginines of (R/W)9 showed to be six time less efficiently internalized, suggesting the importance of arginine residues for the interaction of the conjugate with the membrane. We have also showed that the PNA targeted to the coding region of IGF1R coupled to (R/W)9 is efficiently internalized to prostate cancer cells where it inhibits the expression of the beta chain of the receptor.Les Peptide Nucleic Acids (PNA) sont des oligonuclĂ©otides antisens analogues de lâADN, dont le squelette phosphodiester a Ă©tĂ© remplacĂ© par un squelette pseudo-peptidique dâunitĂ©s 2-aminoĂ©thylglycine, sur lequel sont greffĂ©es des bases azotĂ©es. Des PNA dirigĂ©s contre les ARN messagers peuvent inhiber la traduction in vitro et dans les cellules humaines. Lorsquâils sont dirigĂ©s contre la partie codante du transcrit, des PNA polypyrimidiques peuvent bloquer physiquement lâĂ©longation de la traduction en stoppant la machinerie ribosomale. Le transcrit nâest pas dĂ©gradĂ© et une protĂ©ine tronquĂ©e est gĂ©nĂ©rĂ©e in vitro. Dans le cas de protĂ©ines dont la surexpression conduit Ă des pathologies, des protĂ©ines tronquĂ©es inactives peuvent jouer un rĂŽle de dominant nĂ©gatif dans les cellules. Des protĂ©ines tronquĂ©es de lâInsulin-like Growth Factor-1 (IGF1R), rĂ©cepteur cellulaire surexprimĂ© dans de nombreux cancers, inhibent la tumorigĂ©nĂšse et la rĂ©sistance Ă lâapoptose de cellules cancĂ©reuses. La pĂ©nĂ©tration cellulaire des PNA est la principale limite Ă leur utilisation in vivo et il est nĂ©cessaire de dĂ©velopper des transporteurs efficaces pour ces oligonuclĂ©otides neutres. Les Cell Penetrating Peptides (CPP) sont des peptides naturels ou synthĂ©tiques, qui peuvent ĂȘtre conjuguĂ©s Ă diffĂ©rentes molĂ©cules pour promouvoir leur internalisation cellulaire. Les objectifs de ce travail de thĂšse Ă©taient de comprendre les critĂšres requis pour lâarrĂȘt de lâĂ©longation de la traduction par les PNA et dâĂ©tudier leur internalisation cellulaire mĂ©diĂ©e par le CPP (R/W)9. Nous avons montrĂ© quâun couplage covalent entre ce peptide et deux PNA 13-mer permet lâinternalisation des conjuguĂ©s dans un systĂšme cellulaire rapporteur, conduisant Ă leur activitĂ© biologique en prĂ©sence dâun agent lysosomotropique. Les conjuguĂ©s interagissent avec les glycosaminoglycanes membranaires et sont internalisĂ©s par endocytose en moins dâune heure. De plus, les conjuguĂ©s formĂ©s avec un peptide analogue comportant des lysines sont six fois moins internalisĂ©s, mettant en Ă©vidence lâimportance des rĂ©sidus arginines du peptide (R/W)9 pour lâinteraction avec la membrane. Enfin, nous avons montrĂ© que le peptide (R/W)9 couplĂ© Ă un PNA dirigĂ© contre la sĂ©quence codante de lâIGF1R permet son internalisation dans les cellules de cancer de la prostate et que le conjuguĂ© inhibe spĂ©cifiquement lâexpression de la chaĂźne ÎČ du rĂ©cepteur
Lâaction de Pierre Uri Ă Â la Haute AutoritĂ© de la Ceca
AprĂšs avoir Ă©tudiĂ©, dans le cadre de mon mĂ©moire de maĂźtrise, il y a plusieurs annĂ©es, lâaction de Pierre Uri en faveur de la construction europĂ©enne ainsi que son cheminement personnel en tant quâEuropĂ©en, je crois que je nâavais pas pris toute la mesure de son apport et de lâampleur de son travail. Avec le recul, devenue moi-mĂȘme fonctionnaire et grĂące au travail que jâai effectuĂ© pour prĂ©senter lâaction de Pierre Uri Ă la division Ăconomie de la Ceca, je mesure encore plus la particularit..
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