Associations between sex, body mass index and the individual microglial response in Alzheimer’s disease

Background and objectives 18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer’s disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between β-amyloid-accumulation and microglial activation in AD. Methods 49 patients with AD (29 females, all Aβ-positive) and 15 Aβ-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and β-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional Aβ-PET on TSPO-PET was used to determine the Aβ-plaque-dependent microglial response (slope) and the Aβ-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI). Results In AD, females showed higher mean cortical TSPO-PET z-scores (0.91 ± 0.49; males 0.30 ± 0.75; p = 0.002), while Aβ-PET z-scores were similar. The Aβ-plaque-independent microglial response was stronger in females with AD (+ 0.37 ± 0.38; males with AD − 0.33 ± 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the Aβ-plaque-dependent microglial response was not different between sexes. The Aβ-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the Aβ-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005). Conclusion While microglia response to fibrillar Aβ is similar between sexes, women with AD show a stronger Aβ-plaque-independent microglia response. This sex difference in Aβ-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the Aβ-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD

Courtage sémantique de services de calcul

La recherche de services de calcul qui correspondent aux besoins d'un utilisateur sur une grille de calcul est une activité complexe. L'objet des travaux réalisés consiste à utiliser une description formelle du domaine d'application comportant l'ensemble des données et des opérateurs du domaine ainsi que leurs propriétés. Cette description est effectuée sous forme d'une spécification algébrique. Le courtage consiste alors à effectuer un filtrage modulo la théorie équationnelle associée à la spécification, entre le terme représentant le service souhaité et les termes représentant les services disponibles. Nous proposons et avons implanté deux algorithmes différents inspirés d'un parcours de l'arbre de recherche des solutions contraint par une quantité d'énergie. Nous présentons les domaines applicatifs algèbre linéaire et optimisation et nous nous intéressons au traitement de la combinaison de domaines. Enfin, nous concluons et présentons les perspectives principales de nos travaux.The search for a computing service which corresponds to the user's needs on a grid is a complex activity. The object of this work consists in using a formal description of the dedicated domain : the data, the operators and their properties. This description is carried out as an algebraic specification. Trading then consists in computing an equational matching modulo the theory associated to the specification, between the term representing the required service and the terms representing the available services. We propose two algorithms inspired from a traversal of the solution search tree constrained by an amount of energy. We present some applications in linear algebra and optimization and an interaction between these domain.TOULOUSE-ENSEEIHT (315552331) / SudocSudocFranceF

Reactions of (CF₃)₃BCO with Amines and Phosphines

Reactions of tris(trifluoromethyl)borane carbonyl, (CF3)3BCO, with ammonia yielded either a mixture of [NH4][(CF3)3BC(O)NH2], [NH4][(CF3)3BCN], and [NH4]2[{(CF3)3BC(O)}2NH] or neat [NH4]2[{(CF)BC(O)}NH] depending on the reaction conditions. The salt K[(CF3)3BC(O)NH] was obtained as the sole product from the reaction of NH3 with K[(CF3)BC(O)F]. A simple synthesis for cyanotris(trifluoromethyl)borates, M[(CF)3BCN], was developed by dehydration of M[(CF)3BC(O)NH] (M = [NH4], K) using phosgene. In addition, syntheses of the tris(trifluoromethyl)boron species [(CF3)BC(O)NHnPr]-, [(CF3)3BC(O)NMe]-, and (CF3)BC(O)NMe3, as well as of (CF)BC(O)PMe, were performed. All species were characterized by multinuclear NMR spectroscopy. As far as neat substances resulted, IR and Raman spectra were recorded and their thermal behaviors were studied by differential scanning calorimetry. The interpretation of reaction pathways, structures, and vibrational spectra are supported by DFT calculations. The solid-state structure of K2[{(CF3)BC(O)}NH]·2MeCN was determined by single-crystal X-ray diffraction

Haloacyl complexes of boron, [(CF₃)₃BC(O)Hal]⁻ (Hal = F, Cl, Br, I)

The haloacyltris(trifluoromethyl)borate anions [(CF3)3BC(O)Hal]− (Hal=F, Cl, Br, I) have been synthesized by reacting (CF3)3BCO with either MHal (M=K, Cs; Hal=F) in SO2 or MHal (M=[nBu4N]+, [Et4N]+, [Ph4P]+; Hal=Cl, Br, I) in dichloromethane. Metathesis reactions of the fluoroacyl complex with Me3SiHal (Hal=Cl, Br, I) led to the formation of its higher homologues. The thermal stabilities of the haloacyltris(trifluoromethyl)borates decrease from the fluorine to the iodine derivative. The chemical reactivities decrease in the same order as demonstrated by a series of selected reactions. The new [(CF3)3BC(O)Hal]− (Hal=F, Cl, Br) salts are used as starting materials in the syntheses of novel compounds that contain the (CF3)3B-C fragment. All borate anions [(CF3)3BC(O)Hal]− (Hal=F, Cl, Br, I) have been characterized by multinuclear NMR spectroscopy (11B, 13C, 17O, 19F) and vibrational spectroscopy. [PPh4][(CF3)3BC(O)Br] crystallizes in the monoclinic space group P2/c (no. 13) and the bond parameters are compared with those of (CF3)3BCO and K[(CF3)3BC(O)F]. The interpretation of the spectroscopic and structural data are supported by DFT calculations [B3LYP/6‐311+G(d)]

[(CF₃)₃BCP]⁻ and [(CF₃)₃BCAs]⁻: Thermally Stable Phosphaethynyl and Arsaethynyl Complexes

Make mine a triple: The tetraphenyl phosphonium salts of [(CF3)3BCX]− (X=P, As) are stable even well above room temperature. The synthesis of these first phospha‐ and arsaethynyl complexes of boron from (CF3)3BCO is carried out in two steps (see scheme). The complex [(CF3)3BCAs]− is the first stable anionic arsaalkyne

(PPh₃)₃RhCNB(CF₃)₃ and (PPh₃)₃RhNCB(CF₃)₃: Isocyano- and Cyanoborate Complexes of Tris(triphenylphosphine)rhodium(I)

The reactions of K[(CF3)3BNC] and K[(CF3)3BCN] with (PPh3)3RhCl in ethanol resulted in the rhodium(I) complexes (PPh3)3RhNCB(CF3)3 and (PPh3)3RhCNB(CF3)3, respectively. Their 15N-labeled isotopomers were synthesized from the corresponding borate anions. The complexes were characterized by UV, Raman, and multi-NMR spectroscopy, and the crystal structures were obtained. The spectroscopic and structural data are compared to those of the potassium borates and to related rhodium(I) complexes

Cyano- and isocyanotris(trifluoromethyl)borates: Syntheses, spectroscopic properties, and solid state structures of K[(CF₃)₃BCN] and K[(CF₃)₃BNC]

A two step synthesis to the isocyanotris(trifluoromethyl)borate anion, [(CF3)3BNC]-, and its isomerization to the cyanotris(trifluoromethyl)borate anion, [(CF3)3BCN]-, at temperatures above 150 °C are presented. In the first step (CF3)3BNCH was obtained by reacting (CF3)3BCO with hydrogen cyanide followed by deprotonation of the HCN adduct with Li[N(SiMe3)2] in toluene. The thermal behavior of K[(CF3)3BNC] and K[(CF3)3BCN] were investigated by differential scanning calorimetry (DSC), and K[BF4] was identified as a major solid decomposition product. The enthalpy of the isocyanide−cyanide rearrangement, ΔHiso = −35 ± 4 kJ mol-1, was obtained from DSC measurements, and the activation energy, Ea = 180 ± 20 kJ mol-1, from kinetic measurements. The isomerization was modeled as an intramolecular reaction employing DFT calculations at the B3LYP/6-311+G(d) level of theory yielding a reaction enthalpy of ΔHiso = −36.1 kJ mol-1 and an activation energy of Ea = 155.7 kJ mol-1. The solid-state structures of K[(CF3)3BNC] and K[(CF3)3BCN] were determined by single-crystal X-ray diffraction. Both salts are isostructural and crystallize in the orthorhombic space group Pnma (no. 62). In the crystals the borate anions possess Cs symmetry, while for the energetic minimum C3 symmetry is predicted by DFT calculations. The borate anions have been characterized by IR and Raman spectroscopy as well as by NMR spectroscopy. The assignment of the IR and Raman bands is supported by their calculated wavenumbers and intensities. The spectroscopic and structural properties of both borate anions are compared to the properties of the isoelectronic borane carbonyl (CF3)3BCO and the [B(CF3)4]- anion as well as to those of other related species