Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

On-Surface Covalent Linking of Organic Building Blocks on a Bulk Insulator

Kittelmann M, Rahe P, Nimmrich M, Hauke CM, Gourdon A, Kühnle A. On-Surface Covalent Linking of Organic Building Blocks on a Bulk Insulator. ACS Nano. 2011;5(10):8420-8425.On-surface synthesis in ultrahigh vacuum provides a promising strategy for creating thermally and chemically stable molecular structures at surfaces. The two-dimensional confinement of the educts, the possibility of working at higher (or lower) temperatures in the absence of solvent, and the templating effect of the surface bear the potential of preparing compounds that cannot be obtained in solution. Moreover, covalently linked conjugated molecules allow for efficient electron transport and are, thus, particularly interesting for future molecular electronics applications. When having these applications in mind, electrically insulating substrates are mandatory to provide sufficient decoupling of the molecular structure from the substrate surface. So far, however, on-surface synthesis has been achieved only on metallic substrates. Here we demonstrate the covalent linking of organic molecules on a bulk insulator, namely, calcite. We deliberately employ the strong electrostatic interaction between the carboxylate groups of halide-substituted benzoic adds and the surface calcium cations to prevent molecular desorption and to reach homolytic cleavage temperatures. This allows for the formation of aryl radicals and intermolecular coupling. By varying the number and position of the halide substitution, we rationally design the resulting structures, revealing straight lines, zigzag structures, and dimers, thus providing clear evidence for the covalent linking. Our results constitute an important step toward exploiting on-surface synthesis for molecular electronics and optics applications, which require electrically insulating rather than metallic supporting substrates

Manipulating the Conformation of Single Organometallic Chains on Au(111)

The conformations of organometallic polymers formed via the bottom-up assembly of monomer units on a metal surface are investigated, and the relationship between the adsorption geometry of the individual monomer units, the conformational structure of the chain, and the overall shape of the polymer is explored. Iodine-functionalized monomer units deposited on a Au(111) substrate are found to form linear chain structures in which each monomer is linked to its neighbors via a Au adatom. Lateral manipulation of the linear chains using a scanning tunneling microscope allows the structure of the chain to be converted from a linear to a curved geometry, and it is shown that a transformation of the overall shape of the chain is coupled to a conformational rearrangement of the chain structure as well as a change in the adsorption geometry of the monomer units within the chain. The observed conformational structure of the curved chain is well-ordered and distinct from that of the linear chains. The structures of both the linear and curved chains are investigated by a combination of scanning tunneling microscopy measurements and theoretical calculations

Micrometre-long covalent organic fibres by photoinitiated chain-growth radical polymerization on an alkali-halide surface

On-surface polymerization is a promising technique to prepare organic functional nanomaterials that are challenging to synthesize in solution, but it is typically used on metal substrates, which play a catalytic role. Previous examples on insulating surfaces have involved intermediate self-assembled structures, which face high barriers to diffusion, or annealing to higher temperatures, which generally causes rapid dewetting and desorption of the monomers. Here we report the photoinitiated radical polymerization, initiated from a two-dimensional gas phase, of a dimaleimide monomer on an insulating KCl surface. Polymer fibres up to 1 μm long are formed through chain-like rather than step-like growth. Interactions between potassium cations and the dimaleimide’s oxygen atoms facilitate the propagation of the polymer fibres along a preferred axis of the substrate over long distances. Density functional theory calculations, non-contact atomic force microscopy imaging and manipulations at room temperature were used to explore the initiation and propagation processes, as well as the structure and stability of the resulting one-dimensional polymer fibres

Non-Gaussian dynamics in smectic liquid crystals of parallel hard rods

Using computer simulations, we studied the diffusion and structural relaxation in equilibrium smectic liquidcrystal bulk phases of parallel hard spherocylinders. These systems exhibit a non-Gaussian layer-to-layer diffusion due to the presence of periodic barriers and transient cages and show remarkable similarities with the behavior of out-of-equilibrium supercooled liquids. We detect a very slow interlayer relaxation dynamics over the whole density range of the stable smectic phase which spans a time interval of four time decades. The intrinsic nature of the layered structure yields a hopping-type diffusion which becomes more heterogeneous for higher packing fractions. In contrast, the in-layer dynamics is typical of a dense fluid with a relatively fast decay. Our results on the dynamic behavior agree well with that observed in systems of freely rotating hard rods but differ quantitatively as the height of the periodic barriers reduces to zero at the nematic-smectic transition for aligned rods, while it remains finite for freely rotating rods

Providing internet-based audiological counselling to new hearing aid users

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal