Automation of [18F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin-1 receptor antagonist (rhIL-1RA)

[(18)F]Fluoroacetaldehyde is a biocompatible prosthetic group that has been implemented pre‐clinically using a semi‐automated remotely controlled system. Automation of radiosyntheses permits use of higher levels of [(18)F]fluoride whilst minimising radiochemist exposure and enhancing reproducibility. In order to achieve full‐automation of [(18)F]fluoroacetaldehyde peptide radiolabelling, a customised GE Tracerlab FX‐FN with fully programmed automated synthesis was developed. The automated synthesis of [(18)F]fluoroacetaldehyde is carried out using a commercially available precursor, with reproducible yields of 26% ± 3 (decay‐corrected, n = 10) within 45 min. Fully automated radiolabelling of a protein, recombinant human interleukin‐1 receptor antagonist (rhIL‐1RA), with [(18)F]fluoroacetaldehyde was achieved within 2 h. Radiolabelling efficiency of rhIL‐1RA with [(18)F]fluoroacetaldehyde was confirmed using HPLC and reached 20% ± 10 (n = 5). Overall RCY of [(18)F]rhIL‐1RA was 5% ± 2 (decay‐corrected, n = 5) within 2 h starting from 35 to 40 GBq of [(18)F]fluoride. Specific activity measurements of 8.11–13.5 GBq/µmol were attained (n = 5), a near three‐fold improvement of those achieved using the semi‐automated approach. The strategy can be applied to radiolabelling a range of peptides and proteins with [(18)F]fluoroacetaldehyde analogous to other aldehyde‐bearing prosthetic groups, yet automation of the method provides reproducibility thereby aiding translation to Good Manufacturing Practice manufacture and the transformation from pre‐clinical to clinical production

Les mouvements sociaux à Nice en 1906 et la gestion de la crise par les pouvoirs publics

Suite à la non application de lois sociales promulguées à la fin du XIXe s, les syndicats se mobilisent et font de l’année 1906 une année d’agitation sociale. Ces mouvements sociaux sont très suivis dans les Alpes maritimes et après la manifestation du 1er mai 1906 de nombreux conflits éclatent. Les pouvoirs publics tentent de servir de médiateur, souvent à la demande même des grévistes.Following the non-application on social laws promulgated at the end of XIXth century, trade-unions mobilized their forces and the year of 1906 was particularly agitated socially. These social movements are very followed in Maritim Alps and after 1st may 1906’s manifestation a lot of conflicts appeared. Public power tries to be a mediator, often to the request of strikers

Raphaël Bischoffsheim, entre affairisme et philanthropie, une figure emblématique de la vie politique niçoise de la fin du XIXe siècle

La vie politique niçoise de la fin du XIXe au début du XXe siècle est associée à quelques personnalités, tel Raphaël Bischoffsheim, un riche banquier hollandais, devenu Français en 1880. Député entre 1885 et 1906 à Nice puis à Puget-Théniers, ce personnage controversé a tour à tour été apprécié pour son mécénat en faveur du département et décrié en raison des risques de collusion entre les milieux financiers et politiques.In the city of Nice during the closing period of the 19th century and the beginning of the 20th century, the political life was related to several high personalities, such as Raphaël Bischoffsheim, a rich Dutch banker who took French nationality in 1880. Member of the Assemblée Nationale for Nice then for Puget-Théniers between 1885 and 1906, this controversial man was as well appreciated for its engagement in favor of the “département des Alpes-Maritimes”, and slandered because of the risks of collusion between the financial and political circles

Les mouvements sociaux à Nice en 1906 et la gestion de la crise par les pouvoirs publics

Suite à la non application de lois sociales promulguées à la fin du XIXe s, les syndicats se mobilisent et font de l’année 1906 une année d’agitation sociale. Ces mouvements sociaux sont très suivis dans les Alpes maritimes et après la manifestation du 1er mai 1906 de nombreux conflits éclatent. Les pouvoirs publics tentent de servir de médiateur, souvent à la demande même des grévistes.Following the non-application on social laws promulgated at the end of XIXth century, trade-unions mobilized their forces and the year of 1906 was particularly agitated socially. These social movements are very followed in Maritim Alps and after 1st may 1906’s manifestation a lot of conflicts appeared. Public power tries to be a mediator, often to the request of strikers

Evaluation of \u3csup\u3e18\u3c/sup\u3eF-IAM6067 as a sigma-1 receptor PET tracer for neurodegeneration in vivo in rodents and in human tissue

© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. The sigma 1 receptor (S1R) is widely expressed in the CNS and is mainly located on the endoplasmic reticulum. The S1R is involved in the regulation of many neurotransmission systems and, indirectly, in neurodegenerative diseases. The S1R may therefore represent an interesting neuronal biomarker in neurodegenerative diseases such as Parkinson\u27s (PD) or Alzheimer\u27s diseases (AD). Here we present the characterisation of the S1R-specific 18F-labelled tracer 18F-IAM6067 in two animal models and in human brain tissue. Methods: Wistar rats were used for PET-CT imaging (60 min dynamic acquisition) and metabolite analysis (1, 2, 5, 10, 20, 60 min post-injection). To verify in vivo selectivity, haloperidol, BD1047 (S1R ligand), CM398 (S2R ligand) and SB206553 (5HT2B/C antagonist) were administrated for pre-saturation studies. Excitotoxic lesions induced by intra-striatal injection of AMPA were also imaged by 18F-IAM6067 PET-CT to test the sensitivity of the methods in a well-established model of neuronal loss. Tracer brain uptake was also verified by autoradiography in rats and in a mouse model of PD (intrastriatal 6-hydroxydopamine (6-OHDA) unilateral lesion). Finally, human cortical binding was investigated by autoradiography in three groups of subjects (control subjects with Braak ≤2, and AD patients, Braak \u3e2 & ≤4 and Braak \u3e4 stages). Results: We demonstrate that despite rapid peripheral metabolism of 18F-IAM6067, radiolabelled metabolites were hardly detected in brain samples. Brain uptake of 18F-IAM6067 showed differences in S1R anatomical distribution, namely from high to low uptake: pons-raphe, thalamus medio-dorsal, substantia nigra, hypothalamus, cerebellum, cortical areas and striatum. Pre-saturation studies showed 79-90% blockade of the binding in all areas of the brain indicated above except with the 5HT2B/C antagonist SB206553 and S2R ligand CM398 which induced no significant blockade, indicating good specificity of 18F-IAM6067 for S1Rs. No difference between ipsi- and contralateral sides of the brain in the mouse model of PD was detected. AMPA lesion induced a significant 69% decrease in 18F-IAM6067 uptake in the globus pallidus matching the neuronal loss as measured by NeuN, but only a trend to decrease (-16%) in the caudate putamen despite a significant 91% decrease in neuronal count. Moreover, no difference in the human cortical binding was shown between AD groups and controls. Conclusion: This work shows that 18F-IAM6067 is a specific and selective S1R radiotracer. The absence or small changes in S1R detected here in animal models and human tissue warrants further investigations and suggests that S1R might not be the anticipated ideal biomarker for neuronal loss in neurodegenerative diseases such as AD and PD

Marine epibiosis. II. Reduced fouling on Polysyncraton lacazei (Didemnidae, Tunicata) and proposal of an antifouling potential index

Polysyncraton lacazei is a colonial tunicate (family didemnidae) living in the NW-mediterranean rocky sublitoral. A thorough scanning of numerous colonies revealed that in spite of an apparently heavy local fouling pressure only one fouling species — a kamptozoan — is encountered with some regularity on Polysyncraton. We try to define the epibiotic situation of sessile marine organisms as composed of four epibiotic parameters: longevity or exposure time (A), epibiont load (E), colonizer pool (CP) and fouling-period (FP). Subsequently, these factors are combined to propose an “Antifouling Potential” index: AFP=(1−E/CP)×A/(FP+A). This index is intended to permit evaluating the relative antifouling defense potency to be expected in a given organism in a given epibiotic situation and to compare different cases of epibiosis and fouling

Studies on germ cells. IV. Protoplasmic differentiation in the oocytes of certain Hymenoptera

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50238/1/1050260304_ftp.pd