Base-Paired and Base-Stacked Structures of the Anti-HIV Drug Lamivudine: A Nucleoside DNA-Mimicry with Unprecedented Topology

We have prepared a DNA-mimicry of nucleosides in which the anti-HIV drug lamivudine (beta-L-2',3'-dideoxy-3'-thiacytidine, 3TC) self-assembles into a base-paired and helically base-stacked hexagonal structure. Face-to-face and face-to-tail stacked 3TC=3TC dimers base-paired through two hydrogen bonds between neutral cytosines by either N-H center dot center dot center dot O or N-H center dot center dot center dot N atoms give rise to a right-handed DNA-mimicry of lamivudine with an unusual highly symmetric hexagonal lattice and topology. In addition, a base-paired and base-stacked supramolecular architecture of lamivudine hemihydrochloride hemihydrate was also obtained as a result of our crystal screenings. This structure is formed through partially face-to-face stacked lamivudine pairs held together by protonated and neutral fragments. However, no helical stacking occurs in this structure in which lamivudine also adopts unusual conformations as the C1'-endo and C1'-exo sugar puckers and cytosine orientations intermediate between the anti and syn conformations. As a conclusion drawn from the nucleoside duplex, the hexagonal DNA-mimicry of lamivudine reveals that such double-stranded helices can be assembled without counterions and organic solvents but with higher crystallographic symmetry instead, because only water crystallizes together with lamivudine in this structure.

New Species of the Thorny Catfish Genus Leptodoras (Siluriformes: Doradidae) from Rio Fresco, Xingu Basin, Brazil

A new species of the thorny catfish genus Leptodoras (family Doradidae) is described. The new species shares three characters with its congeners, the modified oral hood with distinct upper labial extensions, the first gill arch with enlarged accessory lamellae extending well onto medial face of gill filaments, and the pelvic fin inserted in anterior half of body. The new species is distinguished from congeners by having a large dark submarginal blotch on distal half of dorsal-fin spine and anteriormost dorsal-fin branched rays, lower labial extension of modified oral hood extending more posteriorly than upper labial extension, relatively few midlateral scutes, gas bladder moderately sized (not reduced), paired bony capsules on anteriormost vertebrae reduced to paired cup-like laminar ossifications separated by a triangular septum, pair of small, swelling-like diverticula on each side of the anterior chamber of gas bladder, a well-developed anterior nuchal plate, and nuchal foramina present. The new species was discovered from a single specimen collected in the rio Fresco, a tributary of the rio Xingu, and is described based on this and on additional material recently collected in the same area. A discussion of its placement within Leptodoras is also presented.

Molecular and Electronic Structure of the Peptide Subunit of Geobacter sulfurreducens Conductive Phi from First Principles

The respiration of metal oxides by the bacterium Geobacter sulfurreducens requires the assembly of a small peptide (the GS pilin) into conductive filaments termed pili. We gained insights into the contribution of the GS pilin to the pilus conductivity by developing a homology model and performing molecular dynamics simulations of the pilin peptide in vacuo and in solution. The results were consistent with a predominantly helical peptide containing the conserved a-helix region required for pilin assembly but carrying a short carboxy-terminal random-coiled segment rather than the large globular head of other bacterial pilins. The electronic structure of the pain was also explored from first principles and revealed a biphasic charge distribution along the pilin and a low electronic HOMO-LUMO gap, even in a wet environment. The low electronic band gap was the result of strong electrostatic fields generated by the alignment of the peptide bond dipoles in the pilin's alpha-helix and by charges from ions in solution and amino acids in the protein. The electronic structure also revealed some level of orbital delocalization in regions of the pilin containing aromatic amino acids and in spatial regions of high resonance where the HOMO and LUMO states are, which could provide an optimal environment for the hopping of electrons under thermal fluctuations. Hence, the structural and electronic features of the pilin revealed in these studies support the notion of a pilin peptide environment optimized for electron conduction.

Synthesis, crystal structure and magnetic properties of the helical oxalate-bridged copper(II) chain {[(CH3)(4)N](2)[Cu(C2O4)(2)] center dot H2O}(n)

The preparation, crystal structure and magnetic properties of a new oxalate-containing copper(II) chain of formula {[(CH3)(4)N](2)]Cu(C2O4)(2)] center dot H2O}(n) (1) [(CH3)(4)N+ = tetramethylammonium cation] are reported. The structure of 1 consists of anionic oxalate-bridged copper(II) chains, tetramethylammoniun cations and crystallization water molecules. Each copper(II) ion in 1 is surrounded by three oxalate ligands, one being bidentate and the other two exhibiting bis-bidenate coordination modes. Although all the tris-chelated copper(H) units from a given chain exhibit the same helicity, adjacent chains have opposite helicities and then an achiral structure results. Variable-temperature magnetic susceptibility measurements of 1 show the occurrence of a weak ferromagnetic interaction through the oxalate bridge [J = +1.14(1)cm(-1), the Hamiltonian being defined as H = -J Sigma nm S-i . S-j]. This value is analyzed and discussed in the light of available magnetostructural data for oxalate-bridged copper(H) complexes with the same out-of-plane exchange pathway. (C) 2012 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Helical buckling of Skyrme-Faddeev solitons

Solitons in the Skyrme-Faddeev model on R-2 x S-1 are shown to undergo buckling transitions as the circumference of the S-1 is varied. These results support a recent conjecture that solitons in this field theory are well-described by a much simpler model of elastic rods.

Evaluation of the efficiencies of helical anchor plates in sand by centrifuge model tests

The uplift capacity of helical anchors normally increases with the number of helical plates. The rate of capacity gain is variable, considering that the disturbance caused by the anchor installation is generally more pronounced in the soil mass above the upper plates than above the lower plates, because the upper soil layers are penetrated more times. The present investigation examines the effect of the number of helices on the performance of helical anchors in sand, based on the results of centrifuge model tests. Uplift loading tests were performed on 12 different types of piles installed in two containers of dry sand prepared with different densities. The measured fractions of the uplift capacity related to each individual helical plate of multi-helix anchors were compared with the fractions predicted by the individual bearing method. The results of this investigation indicate that in double- and triple-helix anchors, the contributions of the second and third plate to the total anchor uplift capacity decreased with the increase of sand relative density and plate diameter. In addition, these experiments demonstrated that the variation of the anchor load-displacement behavior with the number of helices also depends on these parameters.

Self assembly of human septin 2 into amyloid filaments

Septins are a conserved group of GTP-binding proteins that form hetero-oligomeric complexes which assemble into filaments. These are essential for septin function, including their role in cytokinesis, cell division, exocytosis and membrane trafficking. Septin 2 (SEPT2) is a member of the septin family and has been associated with neurofibrillary tangles and other pathological features of senile plaques in Alzheimer's disease. An in silico analysis of the amino acid sequence of SEPT2 identified regions with a significant tendency to aggregate and/or form amyloid. These were all observed within the GTP-binding domain. This was consistent with the experimental identification of a structure rich in beta-sheet during temperature induced unfolding transitions observed for both the full length protein and the GTP-binding domain alone. This intermediate state is characterized by irreversible aggregation and has the ability to bind Thioflavin-T, suggesting its amyloid nature. Under electron microscopy, fibers extending for several micrometers in length could be visualized. The results shown in this study support the hypothesis that single septins, when present in excess or with unbalanced stoichiometries, may be unstable and assemble into amyloid-like structures. (C) 2011 Elsevier Masson SAS. All rights reserved.