Comparison of the pH-induced conformational change of different clostridial neurotoxins

Clostridial neurotoxins are internalized inside acidic compartments, wherefrom the catalytic chain translocates across the membrane into the cytosol in a low pH-driven process, reaching its proteolytic substrates. The pH range in which the structural rearrangement of clostridial neurotoxins takes place was determined by 8-anilinonaphthalene-1-sulfonate and tryptophan fluorescence measurements. Half conformational change was attained at pH 4.55, 4.50, 4.40, 4.60, 4.40, and 4.40 for tetanus neurotoxin and botulinum neurotoxin serotypes /A, /B, /C, /E, and /F, respectively. This similarity indicates the key residues for the conformation transition are strongly conserved. Acidic liposomes support the conformational rearrangement shifting the effect versus higher pH values, whereas zwitterionic liposomes do not. The disulfide bridge linking the light and the heavy chains together needs to be oxidized to allow toxin membrane insertion, indicating that in vivo its reduction follows exposure to the cytosol after penetration of the endosomal membrane.     

Non-cyclopentadienyl zirconium complexes as catalysts for 1-hexene polymerization

The new β-diketonate complexes (hfac)₂ZrCl₂, (hfac)₃ZrCl, hfac = hexafluoroacetylacetonate, and (thd)₂ZrCl₂, thd = 2,2,6,6-tetramethyl-3,5-heptanedionate, have been prepared in good yield by reacting the corresponding β-diketonate thallium complexes with ZrCl₄ in stoichiometric amounts and they have been characterized by elemental analyses and NMR spectra.These complexes and the β-diketonate complexes (acac)₂ZrCl₂, (acac)₃ZrCl and (thd)₃ZrCl have been tested as catalysts in the polymerization of 1-hexene in the presence of N,N′-(dimethylanilinium)-tetrakis(pentafluorophenylborate) or ethyltrichloroacetate as co-catalysts at room temperature using ethyl aluminum sesquichloride as scavenger.     

TOPASE-MED : comment repenser l’imagerie TEP grâce aux détecteurs semiconducteurs

This paper presents the main outcomes of the TOPASE-MED project, a feasibility study of a semiconductor-based PET imaging system, using CdTe as detection material. This project has followed three main goals: dimensioning a CdTe-based imager by simulation, developing technological bricks needed to build such a system and demonstrating experimentally the potential of the technology with a small scale mock-up.     

Computational full electron structure study of biological activity in Cyclophilin A

Cyclosporine (CsA) is widely used in organ transplant patients to help prevent the patient’s body from rejecting the organ. CsA has been shown to be a safe and highly effective immunosuppressive drug that binds with the protein Cyclophilin A (CypA) at active sites. However, the exact mechanism of this binding at the molecular level remains unknown. In this project, we elucidate the binding of CsA to CypA at the molecular level by computing their electron structures and revealing their interactions. We employ a novel technique called electron Computer-Aided Drug Design (eCADD) on the protein’s full electron structure along with its hydrophobic pocket and the perturbation theory of the interaction between two wave functions. We have identified the wave function of CypA, the biological active residues and active atoms of CypA and CsA, the interaction site between CypA and CsA, and the hydrogen bonds in the ligand CsA binding site. All these calculated active residues, active atoms, and hydrogen bonds are in good agreement with recorded laboratory experiments and provide guidelines for designing new ligands of CypA. We believe that our eCADD framework can provide researchers with a cost-efficient new method of drug design based on the full electron structure of proteins.     

How do presynaptic PLA2 neurotoxins block nerve terminals?

Snake presynaptic neurotoxins with phospholipase A2 activity block nerve terminals in an unknown way. Here, we propose that they enter the lumen of synaptic vesicles following endocytosis and hydrolyse phospholipids of the inner leaflet of the membrane. The transmembrane pH gradient drives the translocation of fatty acids to the cytosolic monolayer, leaving lysophospholipids on the lumenal layer. Such vesicles are highly fusogenic and release neurotransmitter upon fusion with the presynaptic membrane, but cannot be retrieved because of the high local concentration of fatty acids and lysophospholipids, which prevents vesicle neck closure.     

Phylogenetic tests of community assembly across regional to continental scales in tropical and subtropical rain forests

Aim To measure and quantify community phylogenetic structure to evaluate how evolutionary, ecological and biogeographic processes have shaped the distributions and assemblage of tropical and subtropical rain forest tree species across local, regional and continental scales. Location Australia. Methods We used 596 assemblage‐level samples and 1137 woody species in rain forest vegetation sampled across two latitude regions (tropics and sub‐tropics) and five distinct areas. Based on this dataset, we obtained and analysed species‐level trait values (for leaf size, seed size, wood density and maximum height at maturity), measures of community phylogenetic structure and species turnover across space (beta) and evolutionary time (phylobeta). Results Phylobeta values showed that at continental scales (i.e. across the latitude regions combined) species replacement, as turnover in assemblages through time, was by more phylogenetically distant (i.e. less closely related) taxa. Within latitude regions replacement was by more closely related taxa. Assemblages of species were more phylogenetically clustered across the whole phylogeny (net relatedness index) and with respect to more recent divergences (nearest related taxon index) where the effects of historic disturbance (climatic oscillations) had been greater, and less clustered in long‐term stable (refugial) locations. Local species composition in the stable wet tropics showed significant phylogenetic evenness, but there was no corresponding evenness in distributions of the ecological traits measured. Main conclusions Despite a shared evolutionary and biogeographic history, the two regions diverged from each other before the development of internal divergences. Phylogenetic evenness is more evident in long‐term stable habitats (refugia) where species interact in conserved niches. Phylogenetic clustering is more evident where recolonization of more highly disturbed areas from historically reduced species pools reflects filtering of species into phylogenetically preferred habitats.