PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory.

Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.

[Dangerous scorpions from Niger]. / Scorpions dangereux du Niger.

Two dangerous scorpion species are responsible for the severe human envenomations in Niger, Leiurus quinquestriatus (H. et E.), the most abundant, and Androctonus aeneas C.L. Koch, less frequent and described in a Sahel country for the first time. Up to now, A. aeneas was known in North Africa only. Its venom is highly toxic for humans, similar to those of the most dangerous species living in Africa, such as L. quinquestriatus and other species belonging to the genus Androctonus, A. australis (L.) and A. mauretanicus (Poc.), for the envenoming treatment of which specific antivenoms are prepared. Taking into account the absence of a specific antivenom for A. aeneas, the paraspecific neutralising effect of these antivenoms should be tested.

[New mass spectrometry techniques applied to the study of venoms]. / Nouvelles techniques de spectrométrie de masse appliquées à l'étude des venins.

Mass spectrometry is a technique for the analysis and very sensitive identification of molecules. It allows one to determine the mass of the studied product, whether pure or in a mixture, and provides some information on its molecular structure. In the particular case of peptides, this method can, under certain conditions, also provide information on the amino acid sequence. There are two complementary methods in mass spectrometry for the study of the biological molecules: i) ionisation by laser desorption assisted by matrix (MALDI) coupled to a mass analyser of the time of flight type (TOF), which is very effective for the direct study of a mixture of products and ii) ionisation by electronebulisation (ESI) coupled to mass analysers of the quadripolar type and time of flight (Qq-TOF), which allows the interfacing between high phase liquid chromatography and mass spectrometry. These two complementary techniques were already used to draw up toxin charts of snake and spider venoms. The purpose is to be able to characterise species based on an actual peptide print of poisonous gland secretions.

Sequence and solution conformation of the 20-residue peptaibols, saturnisporins SA II and SA IV.

Saturnisporins SA II and SA IV are the major components of the 20-residue peptaibol mixture isolated from a culture of the fungus Trichoderma saturnisporum. These peptides exhibit antibiotic activity against Staphylococcus aureus. Their sequences were derived from unequivocal methodology implying the combined use of positive ion FAB mass spectrometry and NMR: the majority of the sequences result from mass spectrometry fragmentations and the location of isomeric residues arises either from analysis of ROESY cross-peaks between contiguous amide protons or from heteronuclear 2J or 3J 1H-13C couplings detected in long-range 1H-13C COSY experiments. The sequence specific 1H and 13C NMR assignments are described. Saturnisporins SA II and SA IV exhibit similar secondary structures, as deduced from their ROESY patterns and 3JNHC alpha H coupling constant values, together with amide hydrogen-deuterium exchange rates and temperature coefficients of amide and carbonyl groups. An overall alpha-helical structure is proposed, maintaining two regions of distortion to this regular structure; i) the N-terminal part, which contains 3(10) and mixed alpha-3(10) turns, and ii) the Aib10-Val15 region, including a Pro residue which accommodates a bend stabilized by two 3(10) H-bonds.

Membrane-modifying properties of the pore-forming peptaibols saturnisporin SA IV and harzianin HA V.

Harzianin HA V and saturnisporin SA IV are alpha-amino isobutyric-containing peptides with 18- and 20-residue chain length, respectively. They were isolated from in vitro cultures of Trichoderma species and their sequences were determined by the combined use of positive ion FAB mass spectrometry and NMR. In organic solvent solution, both peptides exhibited the same predominant alpha-helical secondary structure including a hinge at the level of the central Pro residue, as deduced from NMR data. Their interaction with neutral phospholipid bilayers was shown to induce leakage of the material entrapped in small unilamellar vesicles composed of egg phosphatidylcholine/cholesterol (7/3). When incorporated into neutral planar lipid bilayers, they promoted voltage-gated channels. The concentration- and voltage-dependences of the ionic conductances induced by these peptides were studied in macroscopic current-voltage experiments. Single-channel measurements showed that whilst SA IV developed non-integral multi-open states similar to those induced by alamethicins, but with faster kinetics, the shorter analogue, HA V promoted much smaller-sized conducting aggregates in agreement with macroscopic conductance data.

Tricholongins BI and BII, 19-residue peptaibols from Trichoderma longibrachiatum. Solution structure from two-dimensional NMR spectroscopy.

Two nonadecapeptides, tricholongins BI and BII, which display antifungal and antibacterial activities, have been isolated from in vitro cultures of the fungus Trichoderma longibrachiatum. The peptides were separated by reversed-phase HPLC; their amino acid compositions were determined by gas chromatography and their sequences by positive-ion fast-atom-bombardment mass spectrometry and high-field NMR. These linear peptides, containing mainly hydrophobic L-amino acids, 8-9 2-aminoisobutyric acid residues and exhibiting an acetylated N-terminal residue and an amino alcohol C-terminal leucinol belong to the peptaibol class. The methanol solution structure of tricholongins BI and BII has been investigated using both one- and two-dimensional NMR techniques. The total 1H-NMR and 13C-NMR assignments are given. By a combination of the 3JNH,C alpha H coupling constant values, temperature coefficients of the NH and CO groups, amide hydrogen/deuterium-exchange rate measurements and NOE data, a secondary structure for tricholongins in solution has been proposed. Both peptides adopt a similar alpha-helical conformation with a hinge around Pro13 resulting from two 3(10) bonds. The results suggest that the N-terminus contains mixed alpha/3(10) bonds. The membrane permeability modifications induced by tricholongins have been assayed by the use of liposomes composed of egg phosphatidylcholine with 20-30% cholesterol. The peptide-induced leakage of an entrapped fluorescent probe has been followed by fluorescence spectroscopy. In a concentration range of 0.13-0.31 microM, tricholongins induce the leakage of 50% of the entrapped material in 20 min.

[Not Available]. / Etude analytique des produits lourds du petrole-V Bromation des residus lourds petroliers au moyen d'un reactif original, le tribromure de tetrabutylammonium, et essais preliminaires de determination d'un indice de brome applicable aux fractions lourdes.

A new method of bromine number determination appropriate to heavy-ends petroleum is reported. This method, which uses an electrochemical titration and tetrabutylammonium tribromide as reagent, has been tested on Boscan atmospheric residues. The titration of the unreacted tribromide ions and of the bromide ions produced enables the proportion of the bromine addition to multiple bonds and the proportion of substitution reactions with aromatic compounds (phenols, amines, etc.) to be estimated. The sensitivity and reproducibility of this easy method are both good.