Depletion of SMN by RNA interference in HeLa cells induces defects in Cajal body formation

Neuronal degeneration in spinal muscular atrophy (SMA) is caused by reduced expression of the survival of motor neuron (SMN) protein. The SMN protein is ubiquitously expressed and is present both in the cytoplasm and in the nucleus where it localizes in Cajal bodies. The SMN complex plays an essential role for the biogenesis of spliceosomal U-snRNPs. In this article, we have used an RNA interference approach in order to analyse the effects of SMN depletion on snRNP assembly in HeLa cells. Although snRNP profiles are not perturbed in SMN-depleted cells, we found that SMN depletion gives rise to cytoplasmic accumulation of a GFP-SmB reporter protein. We also demonstrate that the SMN protein depletion induces defects in Cajal body formation with coilin being localized in multiple nuclear foci and in nucleolus instead of canonical Cajal bodies. Interestingly, the coilin containing foci do not contain snRNPs but appear to co-localize with U85 scaRNA. Because Cajal bodies represent the location in which snRNPs undergo 2′-O-methylation and pseudouridylation, our results raise the possibility that SMN depletion might give rise to a defect in the snRNA modification process

Symmetry-selected spin-split hybrid states in C60_{60}/ferromagnetic interfaces

The understanding of orbital hybridization and spin-polarization at the organic-ferromagnetic interface is essential in the search for efficient hybrid spintronic devices. Here, using first-principles calculations, we report a systematic study of spin-split hybrid states of C$_{60}$ deposited on various ferromagnetic surfaces: bcc-Cr(001), bcc-Fe(001), bcc-Co(001), fcc-Co(001) and hcp-Co(0001). We show that the adsorption geometry of the molecule with respect to the surface crystallographic orientation of the magnetic substrate as well as the strength of the interaction play an intricate role in the spin-polarization of the hybrid orbitals. We find that a large spin-polarization in vacuum above the buckyball can only be achieved if the molecule is adsorbed upon a bcc-(001) surface by its pentagonal ring. Therefore bcc-Cr(001), bcc-Fe(001) and bcc-Co(001) are the optimal candidates. Spin-polarized scanning tunneling spectroscopy measurements on single C$_{60}$ adsorbed on Cr(001) and Co/Pt(111) also confirm that both the symmetry of the substrate and of the molecular conformation have a strong influence on the induced spin polarization. Our finding may give valuable insights for further engineering of spin filtering devices through single molecular orbitals.Comment: 10 pages, 9 figure

Tuning the Magnetic Anisotropy at a Molecule-Metal Interface

International audienceWe demonstrate that a C 60 overlayer enhances the perpendicular magnetic anisotropy of a Co thin film, inducing an inverse spin reorientation transition from in plane to out of plane. The driving force is the C 60 =Co interfacial magnetic anisotropy that we have measured quantitatively in situ as a function of the C 60 coverage. Comparison with state-of-the-art ab initio calculations show that this interfacial anisotropy mainly arises from the local hybridization between C 60 p z and Co d z 2 orbitals. By generalizing these arguments, we also demonstrate that the hybridization of C 60 with a Fe(110) surface decreases the perpendicular magnetic anisotropy. These results open the way to tailor the interfacial magnetic anisotropy in organic-material–ferromagnet systems

Molecular-scale dynamics of light-induced spin cross-over in a two-dimensional layer

Spin cross-over molecules show the unique ability to switch between two spin states when submitted to external stimuli such as temperature, light or voltage. If controlled at the molecular scale, such switches would be of great interest for the development of genuine molecular devices in spintronics, sensing and for nanomechanics. Unfortunately, up to now, little is known on the behaviour of spin cross-over molecules organized in two dimensions and their ability to show cooperative transformation. Here we demonstrate that a combination of scanning tunnelling microscopy measurements and ab initio calculations allows discriminating unambiguously between both states by local vibrational spectroscopy. We also show that a single layer of spin cross-over molecules in contact with a metallic surface displays light-induced collective processes between two ordered mixed spin-state phases with two distinct timescale dynamics. These results open a way to molecular scale control of two-dimensional spin cross-over layers

Sustainable computational science: the ReScience initiative

Computer science o ers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results, however computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel con dent their research is reproducible. But this is not exactly true. Jonathan Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. e actual scholarship is the full so ware environment, code, and data that produced the result. is implies new work ows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested, hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically di erent from other traditional scienti c journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and so ware tests

Increasing crop heterogeneity enhances multitrophic diversity across agricultural regions

International audienceAgricultural landscape homogenization has detrimental effects on biodiversity and key ecosystem services. Increasing agricultural landscape heterogeneity by increasing seminatural cover can help to mitigate biodiversity loss. However, the amount of seminatural cover is generally low and difficult to increase in many intensively managed agricultural landscapes. We hypothesized that increasing the heterogeneity of the crop mosaic itself (hereafter “crop heterogeneity”) can also have positive effects on biodiversity. In 8 contrasting regions of Europe and North America, we selected 435 landscapes along independent gradients of crop diversity and mean field size. Within each landscape, we selected 3 sampling sites in 1, 2, or 3 crop types. We sampled 7 taxa (plants, bees, butterflies, hoverflies, carabids, spiders, and birds) and calculated a synthetic index of multitrophic diversity at the landscape level. Increasing crop heterogeneity was more beneficial for multitrophic diversity than increasing seminatural cover. For instance, the effect of decreasing mean field size from 5 to 2.8 ha was as strong as the effect of increasing seminatural cover from 0.5 to 11%. Decreasing mean field size benefited multitrophic diversity even in the absence of seminatural vegetation between fields. Increasing the number of crop types sampled had a positive effect on landscape-level multitrophic diversity. However, the effect of increasing crop diversity in the landscape surrounding fields sampled depended on the amount of seminatural cover. Our study provides large-scale, multitrophic, cross-regional evidence that increasing crop heterogeneity can be an effective way to increase biodiversity in agricultural landscapes without taking land out of agricultural production

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

International audienceThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary car-cinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low-and high-grade lung neuroendocrine neoplasms

Première prise en main de la classe : l’apport de la vidéo-formation

National audienceLe premier contact avec la classe constitue une expérience « initiatique » qui marque le passage du statut d’étudiant à celui d’enseignant. Bien qu’abordée en formation initiale, cette première prise en main apparaît véritablement signifiante à l’enseignant novice lorsqu’il franchit la porte du gymnase

Caractérisation fonctionnelle de signaux et de facteurs impliqués dans la biogénèse des snRNPs

L épissage est un mécanisme assuré par les snRNPs dont la biogénèse est un processus complexe. D abord les snRNAs U1, U2, U4 et U5 sont transcrits dans le noyau par l ARN polymérase II. Après que leur extrémité 5 ait été mono-méthylée, ils sont ensuite exportés vers le cytoplasme où ils s y associent avec les protéines SmB, D1, D2, D3, E, F et G. Cette association est requise pour permettre le recrutement de l hyperméthylase Tgs1 responsable de la triméthylation de la coiffe 5 m7G des snRNAs en méthyl-2,2,7-guanosine (m3G). Ceci génère un signal de localisation nucléaire bipartite, formée par le complexe des protéines Sm et la coiffe m3G, permettant l importation nucléaire de la particule. D autres étapes, comme la modification de résidus interne des snRNAs et l addition de protéines spécifiques vient compléter l assemblage de snRNPs fonctionnelles. Nous avons montré que les extensions C-terminale des protéines SmD1 et SmD3 de mammifères possèdent des propriétés de localisation nucléaires et formeraient avec l extension C-ter de SmB une protubérance basique portant le NLS des protéines Sm. L assemblage des protéines Sm sur les snRNAs est assuré par le complexe SMN. Un niveau réduit de protéine SMN fonctionnelle est corrélé à une pathologie autosomale récessive : l amyotrophie spinale. Nous avons montré que la déplétion par RNAi de la protéine SMN induit une accumulation cytoplasmique de la protéine fusion GFP-SmB, ainsi qu une dissociation des Cajal bodies. D autre part Nous avons caractérisé deux isoformes de l hyperméthylase Tgs1 responsable de la tri-méthylation de la coiffe des snRNAs: Une isoforme pleine longueur principalement cytoplasmique et une isoforme courte retrouvée dans le noyau, produite par clivage protéolytique ubiquitine/protéasome dépendant. Cette dernière interagit avec une protéine de cœur des snoRNPs, la fibrillarine, suggérant qu elle ait un rôle dans leur maturationSplicing is process involving snRNPs of which biogenesis is a complex pathway. In a first step, U1, U2, U4 and U5 snRNA are transcribed by the RNA pol II in the nucleus. Co-transcriptionnally, snRNAs are mono-methylated at their 5 ends and then exported to cytoplasm where they are assembled with SmB, D1, D2, D3, E, F et G proteins. This assembly is required for the further tri-methylation of the 5 cap in methyl-2,2,7-guanosine (m3G) by the Tgs1 hypermethylase. These events generate a bi-partite nuclear localization signal composed of the Sm core complex and the tri-methylated cap. This bi-partite NLS promotes the import back into the nucleus of the newly synthesized snRNP particle. Once in the nucleus the snRNP particle undergoes further maturation events like bases modifications, and specific proteins assembly. In our work, we showed that C-terminal tails of SmD1 and SmD3 proteins possess nuclear localisation properties. We proposed that the C-terminal tails of SmB, SmD1 and SmD3 could form a basic protuberance carrying the nuclear localisation determinant of the Sm core complex. Sm core protein assembly is controlled by the SMN complex. A reduced level of functional SMN has been shown to be responsible of an autosomal recessive disease called Spinal Muscular atrophy (SMA). In our work, by using siRNA approach we showed that SMN depletion induces GFP-SmB fusion protein accumulation in the cytoplasm and a Cajal bodies structure disassembly. In addition, we characterized two isoforms of the Tgs1 hypermethylase: a full length isoform found mainly in the cytoplasm and a short isoform localized in the nucleus, produced by proteolytic clivage in a ubiquitin/proteasome dependent manner. The short Tgs1 isoform interacts with the core snoRNPs protein fibrillarin, suggesting that it could be involved in their maturationMONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Étude de la saturation de gluons dans le cadre du groupe de renormalisatio

La puissance des accélérateurs de particules augmente de telle façon qu'il est de plus en plus nécessaire de connaître précisément les distributions de partons dans le hadron à l'état initial de la collision. Toutefois, on s'est rendu compte que les techniques de resommation logarithmiques connues violent le principe d'unitarité lorsque l'on sonde le proton avec des temps caractéristiques de plus en plus petit. Aussi a-t-on cherché de nouvelles techniques pour l'étude des distributions de partons dans les hadrons. Une de ces techniques due à McLerran et Venugopalan, est basée sur une théorie de Yang-Mills semi-classique pour la chromodynamique quantique, dérivée de la théorie des champs de Weizsäcker-Williams de l'électrodynamique quantique.NANTES-BU Sciences (441092104) / SudocSTRASBOURG-Bib.Central Recherche (674822133) / SudocSudocFranceF