[μ-Bis(diphenyl­phosphan­yl)methane]­tricarbon­yl(μ-p-toluene­sulfonyl­meth­yl isocyanato)(triphenyl­phosphane)ironplatinum(Fe—Pt)

The title compound, [FePt(C9H9NO2S)(C18H15P)(C25H22P2)(CO)3], represents a rare example of an isonitrile-bridged heterobimetallic complex (here Pt and Fe) and is an inter­esting precursor for the preparation of heterodinuclear μ-amino­carbyne complexes, since the basic imine-type N atom of the μ2-C=N–R ligand readily undergoes addition with various electrophiles to afford iminium-like salts. In the crystal, the almost symmetrically bridging μ2-C=N-R ligand (neglecting the different atomic radii of Fe and Pt) is strongly bent towards the Fe(CO)3 fragment, with a C=N-R angle of only 121.1 (4)°

Expanded Interactome of the Intrinsically Disordered Protein Dss1

Summary: Dss1 (also known as Sem1) is a conserved, intrinsically disordered protein with a remarkably broad functional diversity. It is a proteasome subunit but also associates with the BRCA2, RPA, Csn12-Thp1, and TREX-2 complexes. Accordingly, Dss1 functions in protein degradation, DNA repair, transcription, and mRNA export. Here in Schizosaccharomyces pombe, we expand its interactome further to include eIF3, the COP9 signalosome, and the mitotic septins. Within its intrinsically disordered ensemble, Dss1 forms a transiently populated C-terminal helix that dynamically interacts with and shields a central binding region. The helix interfered with the interaction to ATP-citrate lyase but was required for septin binding, and in strains lacking Dss1, ATP-citrate lyase solubility was reduced and septin rings were more persistent. Thus, even weak, transient interactions within Dss1 may dynamically rewire its interactome. : Schenstrøm et al. demonstrate that the disordered protein Dss1 forms a transient intramolecular interaction between the C-terminal helical region and a central hydrophobic region. Proteomics reveal several Dss1-binding proteins, including all PCI-domain protein complexes. The dynamic fold-back structure regulates Dss1 interactions with the mitotic septins and ATP-citrate lyase. Keywords: intrinsically disordered proteins, protein degradation, proteasome, PCI domai

A New High-Throughput Tool to Screen Mosquito-Borne Viruses in Zika Virus Endemic/Epidemic Areas

International audienceMosquitoes are vectors of arboviruses affecting animal and human health. Arboviruses circulate primarily within an enzootic cycle and recurrent spillovers contribute to the emergence of human-adapted viruses able to initiate an urban cycle involving anthropophilic mosquitoes. The increasing volume of travel and trade offers multiple opportunities for arbovirus introduction in new regions. This scenario has been exemplified recently with the Zika pandemic. To incriminate a mosquito as vector of a pathogen, several criteria are required such as the detection of natural infections in mosquitoes. In this study, we used a high-throughput chip based on the BioMark™ Dynamic arrays system capable of detecting 64 arboviruses in a single experiment. A total of 17,958 mosquitoes collected in Zika-endemic/epidemic countries (Brazil, French Guiana, Guadeloupe, Suriname, Senegal, and Cambodia) were analyzed. Here we show that this new tool can detect endemic and epidemic viruses in different mosquito species in an epidemic context. Thus, this fast and low-cost method can be suggested as a novel epidemiological surveillance tool to identify circulating arboviruses

Reappraisal of Vipera aspis Venom Neurotoxicity

BACKGROUND: The variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA(2) neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA(2) composition of the snakes captured in the same areas. [br/] METHODOLOGY/PRINCIPAL FINDINGS: We conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA(2)s. We used SELDI technology to study the diversity of PLA(2) in various venom samples. Neurological signs (mainly cranial nerve disturbances) were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA(2)s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA(2) venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains. [br/] CONCLUSIONS/SIGNIFICANCE: The association of epidemiological studies to genetic, biochemical and immunochemical analyses of snake venoms allowed a good evaluation of the potential neurotoxicity of snake bites. A correlation was found between the expression of neurological symptoms in humans and the intensity of the cross-reaction of venoms with anti-ammodytoxin antibodies, which is correlated with the level of neurotoxin (vaspin and/or ammodytoxin) expression in the venom. The origin of the two recently identified neurotoxic snake populations is discussed according to venom PLA(2) genome and transcriptome data

Selective Regulation of NR2B by Protein Phosphatase-1 for the Control of the NMDA Receptor in Neuroprotection

An imbalance between pro-survival and pro-death pathways in brain cells can lead to neuronal cell death and neurodegeneration. While such imbalance is known to be associated with alterations in glutamatergic and Ca2+ signaling, the underlying mechanisms remain undefined. We identified the protein Ser/Thr phosphatase protein phosphatase-1 (PP1), an enzyme associated with glutamate receptors, as a key trigger of survival pathways that can prevent neuronal death and neurodegeneration in the adult hippocampus. We show that PP1α overexpression in hippocampal neurons limits NMDA receptor overactivation and Ca2+ overload during an excitotoxic event, while PP1 inhibition favors Ca2+ overload and cell death. The protective effect of PP1 is associated with a selective dephosphorylation on a residue phosphorylated by CaMKIIα on the NMDA receptor subunit NR2B, which promotes pro-survival pathways and associated transcriptional programs. These results reveal a novel contributor to the mechanisms of neuroprotection and underscore the importance of PP1-dependent dephosphorylation in these mechanisms. They provide a new target for the development of potential therapeutic treatment of neurodegeneration

Mécanismes de séquestration de la tubuline: etudes biochimiques de l'interaction entre la tubuline et les protéines de la famille de la stathmine.

La stathmine régule la dynamique des microtubules en séquestrant la tubuline dans un complexe constitué de deux hétérodimères de tubuline par molécule de stathmine (complexe T2S). Les autres protéines de la famille de la stathmine peuvent aussi lier deux hétérodimères de tubuline grâce à leur domaine de type stathmine (SLD), mais les différents complexes T2-SLD présentent des stabilités très variables. L’objectif de ce travail a été de comprendre le mécanisme moléculaire conduisant à la formation et à la stabilisation des complexes T2-SLD et les raison de leur diversité. L’analyse de la contribution relative de trois régions de SLD et de leur relation fonctionnelle a apporté des éléments de réponse à ces questions. Grâce à la découverte de peptides issus de SLD s’opposant à la polymérisation de la tubuline et à notre collaboration avec des cristallographes pour résoudre la structure des complexes T2 SLD, ce travail s’inscrit par ailleurs dans le cadre du développement de nouvelles stratégies anticancéreuses visant à perturber la formation du fuseau mitotique

Activation of alkynes by diphosphine- and µ-phosphido-spanned heterobimetallic complexes

International audienc

Mécanismes moléculaires de l'interaction entre la tubuline et les protéines de la famille de la stathmine

La stathmine est une petite phosphoprotéine ubiquiste trés conservée chez les vertébrés. Son expression est régulée au cours de la prolifération et de la différenciation cellulaire, ainsi qu' au cours de certains cancers. La stathminer est aussi l'élément générique d'une famille de protéines qui possèdent toutes un domaine de grande similitude de séquence avec la stathmine (SLD). Les divers SLD séquestrent la tubuline dans un complexe non polymérisable constitué de deux hétérodimères de tubuline par molécule de SLD (T2-SLD) mais avec des stabilités variables. Ce travail de thèse s'inscrit dans le cadre général de la description de ces interactions et de la recherche des raisons de leur diversité. J'ai ainsi tenté de modéliser ces interactions et j'ai étudié le rôle de trois sous-domaines de SLD. Ces travaux ont ..PARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Vieillissement démographique et planification hospitalière en France

Demographic Ageing and Hospital Planning in France. From a Quantitative Appraisal to the Edification of a Space to Negotiate. Since 1970, the health map is essential to the territorialized approach of hospital planning in France. However, three periods can be distinguished, showing its different uses. Initially founded to ensure the equality of the means in the different areas, the sector became a place of coherence between the hospitals, the State and the politicians on the local organization of health care. In the French health system, this evolution expresses the social preference for an equality of means towards equitable procedures for the allowance of resourcesLa carte sanitaire occupe depuis 1970 une place essentielle dans l'approche territorialisée de la planification sanitaire et l'organisation des soins hospitaliers. Trois périodes peuvent être distinguées, montrant la diversité des usages de la carte dans la gestion du système de soins depuis 1970. Initialement fondé pour assurer l'égalité géographique des moyens, le secteur est devenu lieu de cohérence entre les différentes spécialités médicales, puis lieu de débat et d'échange sur l'organisation locale des soins. Dans cette évolution, le vieillissement démographique n'apparaît pas comme un déterminant principal de l'organisation des soins hospitaliers.Jourdain Alain, de Turenne Isabelle. Vieillissement démographique et planification hospitalière en France. In: Espace, populations, sociétés, 2000-3. Le vieillissement dans le monde. pp. 451-460

L'éthique et l'industrie pharmaceutique : un difficile équilibre à trouver

Colloque d'Alexandrie 2005 en hommage à Philippe Fouchar