15 research outputs found
Ancient genomes reveal origin and rapid trans-Eurasian migration of 7<sup>th</sup> century Avar elites
The Avars settled the Carpathian Basin in 567/68 CE, establishing an empire lasting over 200 years. Who they were and where they came from is highly debated. Contemporaries have disagreed about whether they were, as they claimed, the direct successors of the Mongolian Steppe Rouran empire that was destroyed by the Turks in ∼550 CE. Here, we analyze new genome-wide data from 66 pre-Avar and Avar-period Carpathian Basin individuals, including the 8 richest Avar-period burials and further elite sites from Avar’s empire core region. Our results provide support for a rapid long-distance trans-Eurasian migration of Avar-period elites. These individuals carried Northeast Asian ancestry matching the profile of preceding Mongolian Steppe populations, particularly a genome available from the Rouran period. Some of the later elite individuals carried an additional non-local ancestry component broadly matching the steppe, which could point to a later migration or reflect greater genetic diversity within the initial migrant population.- Introduction - Results -- Ancient DNA dataset and quality control -- The genomic structure of the pre-Avar-period population -- The genomic structure of the Avar-period population -- Modeling the eastern steppe ancestry of the elites in the core of the Avar empire -- The heterogeneous ancestry in the regions surrounding the Avar empire’s core - Discussion -- Limitations of the study - Star Method
Synthesis and complexation properties of DTPA-N,N″-bis[bis(n-butyl)]-N′-methyl-tris(amide). Kinetic stability and water exchange of its Gd 3+ complex
International audienceA novel DTPA-tris(amide) derivative ligand, DTPA-N,N''-bis[bis(n-butyl)]-N'-methyl-tris(amide)(H2L3) was synthesized. With Gd3+, it forms a positively charged [Gd(L3)]+ complex, whereas with Cu2+ and Zn2+ [ML3], [MHL3]+ and [M2L3]2+ species are formed. The protonation constants of H2L3 and the stability constants of the complexes were determined by pH potentiometry. The stability constants are lower than those for DTPA-N,N''-bis[bis(n-butyl)amide)](H3L2), due to the lower negative charge and reduced basicity of the amine nitrogens in (L3)2-. The kinetic stability of [Gd(L3)]+ was characterised by the rates of metal exchange reactions with Eu3+, Cu2+ and Zn2+. The exchange reactions, which occur via proton and metal ion assisted dissociation of [Gd(L3)]+, are significantly slower than for [Gd(DTPA)]2-, since the amide groups cannot be protonated and interact only weakly with the attacking metal ions. The relaxivities of [Gd(L2)] and [Gd(L3)]+ are constant between 10-20 degrees C, indicating a relatively slow water exchange. Above 25 degrees C, the relaxivities decrease, similarly to other Gd3+ DTPA-bis(amide) complexes. The pH dependence of the relaxivities for [Gd(L3)]+ shows a minimum at pH approximately 9, thus differs from the behaviour of Gd3+-DTPA-bis(amides) which have constant relaxivities at pH 3-8 and an increase below and above. The water exchange rates for [Gd(L2)(H2O)] and [Gd(L3)(H2O)]+, determined from a variable temperature (17)O NMR study, are lower than that for [Gd(DTPA)(H2O)]2-. This is a consequence of the lower negative charge and decreased steric crowding at the water binding site in amides as compared to carboxylate analogues. Substitution of the third acetate of DTPA5- with an amide, however, results in a less pronounced decrease in kex than substitution of the first two acetates. The activation volumes derived from a variable pressure (17)O NMR study prove a dissociative interchange and a limiting dissociative mechanism for [Gd(L2)(H2O)] and [Gd(L3)(H2O)]+, respectively
Physicochemical and MR imaging characterisation of Gd3+ loaded PAMAM and hyperbranched dendrimers
Synthesis and complexation properties of DTPA-N,N?-bis[bis(n-butyl)]-N?-methyl-tris(amide). Kinetic stability and water exchange of its Gd3+ complex
Synthesis and complexation properties of DTPA-N,N″-bis[bis(n-butyl)]-N′-methyl-tris(amide). Kinetic stability and water exchange of its Gd 3+
Interleukin-1β (187–207)-Induced Hyperthermia is Inhibited by Interleukin-1β (193–195) in Rats
Comparison of a Tartaric Acid Derived Polymeric MRI Contrast Agent to a Small Molecule Model Chelate
Macromolecular ligands for gadolinium MRI contrast agents
Macromolecular ligands for gadolinium contrast agents (CAs) were prepared via a “grafting to” strategy. Copolymers of oligoethylene glycol methyl ether acrylate (OEGA) and an activated ester monomer, pentafluorophenyl acrylate (PFPA), were synthesized and modified with the 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2) chelate for the complexation of Gd3+. The relaxivity properties of the ligated Gd3+ agents were then studied to evaluate the effect of macromolecular architecture on their behavior as magnetic resonance imaging (MRI) CAs. Ligands made from linear and hyperbranched macromolecules showed a substantially increased relaxivity in comparison to existing commercial Gd3+ MRI contrast agents. In contrast, star nanogel polymers exhibited a slightly lower relaxivity per Gd3+ ion (but still substantially higher relaxivity than existing low molecular weight commercial CAs). This work shows that macromolecular ligands have the potential to serve as components of Gd MRI agents as there are enhanced effects on relaxivity, allowing for lower Gd concentrations to achieve contrast, while potentially imparting control over pharmacokinetics