Tetracycline prevents Aβ oligomer toxicity through an atypical supramolecular interaction

The antibiotic tetracycline was reported to possess an anti-amyloidogenic activity on a variety of amyloidogenic proteins both in in vitro and in vivo models. To unveil the mechanism of action of tetracycline on Aβ1-40 and Aβ1-42 at both molecular and supramolecular levels, we carried out a series of experiments using NMR spectroscopy, FTIR spectroscopy, dynamic laser light-scattering (DLS) and atomic force microscopy (AFM). Firstly we showed that the co-incubation of Aβ1-42 oligomers with tetracycline hinders the toxicity towards N2a cell lines in a dose-dependent manner. Therefore, the nature of the interaction between the drug and Aβ oligomers was investigated. To carry out NMR and FTIR studies we have prepared Aβ peptide solutions containing assemblies ranging from monomers to large oligomers. Saturation transfer difference (STD) NMR experiments have shown that tetracycline did not interact with monomers at variance with oligomers. Noteworthy, in this latter case we observed that this interaction was very peculiar since the transfer of magnetization from Aβ oligomers to tetracycline involved all drug protons. In addition, intermolecular cross-peaks between tetracycline and Aβ were not observed in NOESY spectra, indicating the absence of a specific binding site and suggesting the occurrence of a supramolecular interaction. DLS and AFM studies supported this hypothesis since the co-dissolution of Aβ peptides and tetracycline triggered the immediate formation of new aggregates that improved the solubility of Aβ peptides, preventing in this way the progression of the amyloid cascade. Moreover, competitive NMR binding experiments showed for the first time that tetracycline competes with thioflavin T (ThT) in the binding to Aβ peptides. Our data shed light on a novel mechanism of anti-amyloidogenic activity displayed by tetracycline, governed by hydrophobic and charge multiparticle interactions.     

Anionic surfmers in mini-emulsion polymerisation

Mini-emulsion polymerisation of styrene or methylmethacrylate, initiated with ammonium persulphate, have been carried out, in the presence of hexadecane or of polymethylmethacrylate as hydrophobic costabilizer, and the simple hemiester of linear dodecyl alcohol and maleic anhydride, or polymerisable surfactants (surfmers) derived from the condensation of succinic anhydride and either hydroxy propylmethacrylate (MAES), or hydroxyethylmethacrylate (ABS). While the pure surfmers have not so good surface activity, from surface tension measurements, stable mini-emulsion droplets are obtained using a mixture with low amounts of SDS, which have diameters of about 100–200 nm, which remain stable upon polymerisation. Most of the surfmers remain grafted onto the particle surface, thus conferring to these particles strong stability in the various tests. However, due to the high water solubility of the surfmers, another part remains in the serum as unconverted monomer or water-soluble polymers. To cite this article: A. Guyot et al., C.R. Chimie 6 (2003).     

Difference frequency generation in GaAs microdisks

Semiconductor-based whispering-gallery-mode microcavities are very promising for nonlinear optics applications, thanks to the high optical quality factors attainable with today's technology. We propose to exploit this advantage to generate cw light through phase-matched difference frequency generation in a triply resonant GaAs microdisk. A proper choice of the microdisk radius and thickness allows one to select the generated wavelength in the band of 2.5-2.9 mum. Besides illustrating the design features, we numerically show that temperature can be effectively used to compensate for wavelength shifts induced on the generated field by fabrication errors.     

Giant optical anisotropy in single InAs quantum dots

We present the experimental evidence of giant optical anisotropy in single InAs QDs. Polarization-resolved photoluminescence spectroscopy in single QDs reveals a linear polarization ratio which fluctuates, from one dot to another, in sign and in magnitude with absolute values up to 82%. We do not observe any dependence of the linear polarization on incident power and temperature.     

Multilevel structuring of ganglioside-containing aggregates: From simple micelles to complex biomimetic membranes

We revisit the structural investigation we performed over the years on gangliosides, biological amphiphiles typically found in the cell membranes of the nervous system of mammalians. Their molecular features, a large and charged saccharidic headgroup connected to a sticky and extended ceramide double tail, strongly dictate their aggregation properties and place ganglioside aggregates at the borderline between the curved world and the flatland. All along we found that unexpected interesting behaviours were induced by the hierarchical propagation of such extreme monomer properties, from the aggregate scale to the mesoscopic phases. In fact, even small changes in the monomer geometry or hindrance result in dramatic aggregate reshaping, due to collective amplification. Surface packing optimization requires preferential mutual orientation of headgroups, giving rise to trapped solid-disordered configurations. The interplay between interparticle and intraparticle interactions gives rise to unexpected behaviours and counterintuitive phase's landscape. In situ modification of monomer properties, operated by enzymatic digestion of aggregated ganglioside headgroups, either causes collective rearrangement or is overwhelmed by collective trapping, depending on their surface density. This aspect is interesting as gangliosides are not evenly distributed in cell membranes, but only in the outer leaflet, where they p]articipate in rafts, functional microdomains enriched in special lipids including cholesterol. We recently found that ganglioside GM1 forces a preferential distribution of cholesterol, constituting a collective structural pair across the membrane. In summary, ganglioside assemblies, through cooperativity, reach a structural complexity comparable or even bigger and more adaptive than that of a protein.     

Molecular structure, nuclear quadrupole coupling constant and dipole moment of nitrogen trichloride from microwave spectroscopy

The rotational constants of four isotopic species of nitrogen trichloride have been obtained from transitions in the millimeter region. Two r_s structures have been obtained with the following average values of the parameters. rN−C1=1.7535 ± 0.0020 A.The Stark effect of the J = 3 ← 2 transition was analyzed to obtaine the value 0.39 ± 0.01 D for the dipole moment of NCl₃. The measurement of the separation of the two strongest hyperfine components of the J = 2 ← 1 transition yielded the value of −108 ± 3 MHz for the N---Cl bond axis quadrupole coupling constant.     

Determination of the cubic force field of nitrosyl fluoride by vibration-rotation α constants and sextic centrifugal distortion constants

Summary The rotational spectra of ONF in the (100), (010) and (001) excited vibrational states were observed and the corresponding vibrationratation α constants determined. A centrifugal-distortion analysis of 156 ground-state rotational transitions yielded accurate values of all the sextic centrifugal-distortion constants. Both vibration-rotation α constants and sextic centrifugal-distortion constants were used to determine, by least-squares methods, the cubic part of the general valence force field of nitrosyl fluoride. Anab initio calculation provided reliable constraints for the three cubic terms of the potential-energy function which are not directly determinable by the available experimental data. Supporting organizations: C.N.R. and M.P.I.     

Regiochemical control of the ring opening of 1,2-Epoxides by means of chelating processes. 11. Ring opening reactions of aliphatic mono- and difunctionalized cis and trans 2,3- and 3,4-Epoxy Esters

The regiochemical outcome of the ring opening of 1,2-epoxides through chelation processes assisted by metal ions, was verified in the azidolysis of simple aliphatic cis and trans 2,3- and 3,4-epoxy esters and in the corresponding derivatives bearing an ether functionality (OBn) in an allylic relationship to the oxirane ring. The results indicate that the behavior of these epoxides is influenced both by the opening conditions (standard or metal-assisted) and the promoting metal salt [LiClO₄ or Mg(ClO₄)₂].     

Determination of the dipole moment of nitrosyl fluoride in the (001) and (101) states by combination of microwave and laser stark data.

The combination of microwave measurements of the Stark effect in the (001) excited vibrational state with fourteen laser Stark transitions of the hot band (101) ← (001), previously reported in the literature, yielded the values of the dipole moment of ONF both in the (001) and (101) states.