Upslope movements and large scale expansions: the taxonomy and biogeography of the Coenonympha arcania –C. d arwiniana –C. gardetta butterfly species complex

Sibling species groups are suitable models for the understanding of inter‐ and intraspecific processes in taxonomy and biogeography. We analysed 262 individuals from the Alps of the Coenonympha arcania/gardetta species complex by allozyme electrophoresis. These taxa showed high variance amongst populations (F_ST: 0.391) and strong intertaxon genetic differentiation (F_CT: 0.376). Although morphologically similar, Coenonympha gardetta and Coenonympha arcania clearly differ in their genetic characteristics; the morphologically intermediate taxa Coenonympha darwiniana darwiniana and Coenonympha darwiniana macromma are genetically well distinguished from each other and the two other taxa. Coenonympha arcania and C. d. macromma most probably share a common ancestor and evolved by cladogenesis, whereas the taxonomic situation of C. d. darwiniana is still unresolved: This taxon might be the result of hybridization between C. arcania and C. gardetta or it might have a common ancestor together with C. gardetta. We suggest species rank for all four taxa. The distribution of genetic diversity of these populations and the differentiation amongst populations suggest rather different biogeographical scenarios: C. arcania most probably is of Mediterranean origin with postglacial range expansion northwards; C. gardetta survived the last ice age in peripheral refugia of the Alps and has spread all over this high mountain system in the postglacial; C. darwiniana and C. macromma survived the Würm in geographic proximity to their actual distribution areas and only have performed moderate uphill translocations during postglacial warming. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 159 , 890–904.     

Conformational and stacking properties of 3′–5′ and 2′–5′ linked oligoribonucleotides studied by CD

Comparative CD studies have been carried out to characterize the properties of 2′–5′ and 3′–5′ oligoriboadenylates and oligoribouridylates from dimer to decamer. The CD band of the 3′–5′ oligoribonucleotides was larger than that of the 2′–5′ oligoribonucleotides and increased with the increase in chain length, while the CD band of the 2′–5′ oligoribonucleotides increased little beyond the dimer level. The CD analysis of the chain length dependency revealed that the 3′–5′ oligoribonucleotides adopt mainly the base-base stacking interaction, while the base-sugar interaction is predominant in the 2′–5′ oligoribonucleotides. The CD intensity of 3′–5′ oligoribonucleotides decreased to a larger extent at elevated temperatures or in the presence of ethanol compared to that of the 2′–5′ counterparts. Mg²⁺ or Mn²⁺ ion enhanced the magnitude of the CD of 3′–5′ octariboadenylate, while a small decrease in the CD was observed by the presence of Mg²⁺ or Mn²⁺ ion to the 2′–5′ octariboadenylate. The 3′–5′ oligoribonucleotide is likely conformationally flexible and can form helical ordered structure with strong base-base stacking depending on changes in the environment such as temperature, the presence of Mg²⁺ ion, or hydrophobicity of the solution. © 1996 John Wiley & Sons, Inc.     

Asymmetric catalysis of homo‐coupling of 3‐substituted naphthylamine and hetero‐coupling with 3‐substituted naphthol leading to 3,3′‐dimethyl‐2,2′‐diaminobinaphthyl and ‐2‐amino‐2′‐hydroxybinaphthyl

Optically active 3,3′‐dimethyl‐2,2′‐diamino‐1,1′‐binaphthyl (DM‐DABN) and 3,3′‐dimethyl‐2‐amino‐2′‐hydroxybinaphthyl (DM‐NOBIN) derivatives were synthesized by Cu‐(?)‐sparteine complex‐catalyzed enantioselective homo‐ and hetero‐coupling of 2‐naphthylamine, respectively. The difference in enantioselectivity was observed by changing the concentration of oxygen. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Investigating the binding of β‐1,4‐galactan to Bacillus licheniformis β‐1,4‐galactanase by crystallography and computational modeling

Microbial β‐1,4‐galactanases are glycoside hydrolases belonging to family 53, which degrade galactan and arabinogalactan side chains in the hairy regions of pectin, a major plant cell wall component. They belong to the larger clan GH‐A of glycoside hydrolases, which cover many different poly‐ and oligosaccharidase specificities. Crystallographic complexes of Bacillus licheniformis β‐1,4‐galactanase and its inactive nucleophile mutant have been obtained with methyl‐β(1→4)‐galactotetraoside, providing, for the first time, information on substrate binding to the aglycone side of the β‐1,4‐galactanase substrate binding groove. Using the experimentally determined subsites as a starting point, a β(1→4)‐galactononaose was built into the structure and subjected to molecular dynamics simulations giving further insight into the residues involved in the binding of the polysaccharide from subsite ?4 to +5. In particular, this analysis newly identified a conserved β‐turn, which contributes to subsites ?2 to +3. This β‐turn is unique to family 53 β‐1,4‐galactanases among all clan GH‐A families that have been structurally characterized and thus might be a structural signature for endo‐β‐1,4‐galactanase specificity. Proteins 2009. © 2008 Wiley‐Liss, Inc.     

Syntheses and anti‐tubercular activity of β‐substituted and α,β‐disubstituted peptidyl β‐aminoboronates and boronic acids

Tuberculosis is still affecting millions of people worldwide, and new resistant strains of Mycobacterium tuberculosis are being found. It is therefore necessary to find new compounds for treatment. In this paper, we report the synthesis and in vitro testing of peptidyl β‐aminoboronic acids and β‐aminoboronates with anti‐tubercular activity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

The role of the C(2) configuration and methyl substitution on the catalytic activity of novel 2,3,3‐ and 2,7,7‐trimethyl‐substituted γ‐aminonorbornan‐2‐ols

A new set of optically active 2,3,3‐ and 2,7,7‐trimethyl‐substituted γ‐aminonorbornan‐2‐ols have been obtained from 2‐methylenenorbornane‐1‐carbonitriles derived from (+)‐camphor and (?)‐fenchone and probed as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde. This has allowed the study of the structural factors influencing the chirality transfer, such as variation of the relative configuration at C(2) and steric hindrance at C(2), C(3), and C(7) positions of norbornane, which result in the observance of the important role played by the gem‐dimethyl position in γ‐aminonorbornan‐2‐exo‐ols. An empirical rationalization of the obtained experimental results has been realized on the basis of energetically‐favored diastereomeric Noyori‐like transition states. Chirality 2010. © 2010 Wiley‐Liss, Inc.     

The β‐sheet breakers and π‐stacking

Fibrillation of β‐amyloid is recognized as a key process leading to the development of Alzheimer's disease. Small peptides called β‐sheet breakers were found to inhibit the process of β‐amyloid fibrillation and to dissolve amyloid fibrils in vitro, in vivo, and in cell culture studies [1,2]. The mechanism by which peptide inhibition takes place remains elusive and a detailed model needs to be established. Here, we present new insights into the possible role of consecutive Phe residues, present in the structure of β‐sheet breakers, supported by the results obtained by means of MD simulations. We performed a 30‐ns MD of two β‐sheet breakers: iAβ5 (LPFFD) and iAβ6 (LPFFFD) which have two and three consecutive Phe residues, respectively. We have found that Phe rings in these peptides tend to form stacked conformations. For one of the peptides – iAβ6 – the calculated electrostatic contribution to free energy of one of the conformers with three rings stacked (c2) is significantly lower than that corresponding to the unstacked one (c1), two rings stacked (c0) and second conformer with three rings stacked (c3). This may favor the interaction of the c2 conformer with the target on amyloid fibril. We hypothesize that the mechanism of inhibition of amyloidogenesis by β‐sheet breaker involves competition among π‐stacked Phe residues of the inhibitor and π‐stacking within the β‐amyloid fibril. iAβ6 may be a promising candidate for a lead compound of amyloidogenesis inhibitors. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]

It was shown that racemic (±)‐ 2 [1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine], WMS‐1813 ] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ₁ receptors. To study the pharmacological activity of the enantiomers of 2 , a preparative HPLC separation of (R)‐2 and (S)‐2 was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [³H]‐(+)‐pentazocine, (S)‐2 was thrice more potent than its (R)‐configured enantiomer (R)‐2 . The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of (R)‐2 . The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2 . Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Synthesis and optical resolution of 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole‐2‐carboxylic acid

Site selective mono‐ and dimetalation methods have been developed for the functionalization of 1‐[(1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole. Optical resolution of the prepared 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]pyrrole‐2‐carboxylic acid provided new atropisomeric 1‐arylpyrrole derivatives. The absolute configuration of the pure dicarboxylic acid enantiomers was determined by single crystal X‐ray diffraction and CD spectroscopy. Chirality 2009. © 2009 Wiley‐Liss, Inc.     

Role of 5′‐ and 3′‐untranslated regions of mRNAs in human diseases

Protein synthesis is often regulated at the level of initiation of translation, making it a critical step. This regulation occurs by both the cis‐regulatory elements, which are located in the 5′‐ and 3′‐UTRs (untranslated regions), and trans‐acting factors. A breakdown in this regulation machinery can perturb cellular metabolism, leading to various physiological abnormalities. The highly structured UTRs, along with features such as GC‐richness, upstream open reading frames and internal ribosome entry sites, significantly influence the rate of translation of mRNAs. In this review, we discuss how changes in the cis‐regulatory sequences of the UTRs, for example, point mutations and truncations, influence expression of specific genes at the level of translation. Such modifications may tilt the physiological balance from healthy to diseased states, resulting in conditions such as hereditary thrombocythaemia, breast cancer, fragile X syndrome, bipolar affective disorder and Alzheimer's disease. This information tends to establish the crucial role of UTRs, perhaps as much as that of coding sequences, in health and disease.     

Inhibition of UVR‐Induced Tanning and Immunosuppression by Topical Applications of Vitamins C and E to the Skin of Hairless (hr/hr) Mice 1

Exposure of C3HBYB/Wq hairless (hr/hr) mice to ultra‐violet radiation (UVR) for 15 days induced intense tanning of their dorsal skin. Small, dark freckles appeared first, gradually enlarging and coalescing as treatment progressed yielding a uniform tan. Histologically, the gross changes in skin color were matched initially by the appearance of scattered epidermal melanocytes that subsequently proliferated to form discrete, progressively expanding and abutting populations resulting in a uniform melanocyte network throughout the basal layer of the interfollicular epidermis. In contrast, when applied topically before each daily exposure to UVR, a cream or lotion vehicle containing both vitamins C and E (Vits C/E) inhibited UVR‐induced erythema and tanning. Application of Vits C/E, both before and after irradiation, was no more effective in providing photoprotection than pre‐treatment only. At the tissue level, UVR‐induced proliferation and melanogenesis of melanocytes were reduced compared with irradiated controls. The density of individual melanocyte populations was reduced, as was the number of melanocyte populations achieving merger (confluence) with others. Confluence grades and cell counts, estimating the maximum density of melanocyte populations in UVR–Vits C/E‐treated mice, were approximately two thirds those of UVR–vehicle‐treated controls. However, tanning was only one fifth that of UVR–vehicle‐treated controls, suggesting that melanogenesis was also inhibited. In addition to its inhibitory actions on irradiated melanocytes, Vits C/E also inhibited UVR‐induced suppression of contact hypersensitivity (CHS) in haired (Hr/hr) and hr/hr mice of the C3HBYB/Wq strain. The common denominators for most, if not all, of the influences of topically‐applied Vits C/E in muting the responses of the melanocyte and immune systems to UVR may stem from the vitamins’ combined ability to suppress UVR‐stimulated inflammation and its associated cascade of mediators.     

Synthesis of 8‐Substituted 2′‐Deoxyisoguanosines via Unprotected 8‐Brominated 2‐Amino‐2′‐deoxyadenosine

A variety of applications of 8‐alkynylated nucleosides has prompted the synthesis of new purine analogues. Bromination of unprotected 2‐amino‐2′‐deoxyadenosine with Br₂/AcOH/AcONa gives 2‐amino‐8‐bromo‐2′‐deoxyadenosine (87%). The brominated derivative is converted to 8‐alkynylated 2‐amino‐2′‐deoxyadenosines by palladium‐catalyzed Sonogashira cross‐coupling reaction via microwave assistance (81 – 95%). The resulting compounds are further transformed to 8‐alkynylated 2′‐deoxyisoguanosines (52 – 70%). The physical properties of new compounds are investigated.     

Oxygen Ion Diffusion and Surface Exchange Properties of the α‐ and δ‐phases of Bi2O3

Fast oxide ion conduction is a highly desirable property for materials in a wide range of applications. The fastest reported ionic conductor, representing the current state of the art and an oft‐proposed effective limit of oxide ion conductivity, is the high temperature fluorite‐structured δ phase of Bi₂O₃. Here, the ionic nature of this conduction is, for the first time, directly determined through oxygen tracer diffusion measurements. This phase also presents a remarkably high oxygen surface exchange coefficient, competitive with the highest performance solid oxide fuel cell (SOFC) cathodes yet counterintuitively in a material with negligible electronic conduction. The low temperature α‐Bi₂O₃ polymorph is also investigated, revealing a remarkable drop in diffusivity of over 7 orders of magnitude with a temperature drop of just ≈150 °C. Surprisingly, the diffusion studies also reveal a secondary, significantly faster migration pathway in the α phase. This is attributed to grain boundary conduction and shown to be 3–4 orders of magnitude higher than in the bulk. This previously unobserved property could present an exciting opportunity to tailor ionic conductivity levels through manipulating microstructure down to the nanoscale.     

Biosynthesis of the leucine derived α‐, β‐ and γ‐hydroxynitrile glucosides in barley (Hordeum vulgare L.)

Barley (Hordeum vulgare L.) produces five leucine‐derived hydroxynitrile glucosides (HNGs), of which only epiheterodendrin is a cyanogenic glucoside. The four non‐cyanogenic HNGs are the β‐HNG epidermin and the γ‐HNGs osmaronin, dihydroosmaronin and sutherlandin. By analyzing 247 spring barley lines including landraces and old and modern cultivars, we demonstrated that the HNG level varies notably between lines whereas the overall ratio between the compounds is constant. Based on sequence similarity to the sorghum (Sorghum bicolor) genes involved in dhurrin biosynthesis, we identified a gene cluster on barley chromosome 1 putatively harboring genes that encode enzymes in HNG biosynthesis. Candidate genes were functionally characterized by transient expression in Nicotiana benthamiana. Five multifunctional P450s, including two CYP79 family enzymes and three CYP71 family enzymes, and a single UDP‐glucosyltransferase were found to catalyze the reactions required for biosynthesis of all five barley HNGs. Two of the CYP71 enzymes needed to be co‐expressed for the last hydroxylation step in sutherlandin synthesis to proceed. This observation, together with the constant ratio between the different HNGs, suggested that HNG synthesis in barley is organized within a single multi‐enzyme complex.