Interlayer Magnetic Coupling for Fe/Si Multilayers

The antiferromagnetic (AFM) interlayer exchange coupling for sputtered Fe/Si multilayers have been studied by magnetometry, wide-angle neutron diffraction, and spin-polarized neutron reflectometry. Ferromagnetic resonance and Raman scattering measurements have been applied for the characterization of the multilayers. To look for a possible modification of exchange coupling when Si is replaced by Ge, similar Fe/Ge multilayers have been prepared by the same technique. No AFM coupling has been found for Fe/Ge system. Present results differ in part from the literature data and suggest an influence of the sample preparation on the details of its magnetic properties.     

A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation and inhibits replication of a chimeric poliovirus under translational control of the HCV IRES element

Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis and cirrhosis of the liver and has been linked to development of hepatocellular carcinoma. We previously identified a small yeast RNA (IRNA) capable of specifically inhibiting poliovirus (PV) internal ribosome entry site (IRES)-mediated translation. Here we report that IRNA specifically inhibits HCV IRES-mediated translation both in vivo and in vitro. A number of human hepatoma (Huh-7) cell lines expressing IRNA were prepared and characterized. Constitutive expression of IRNA was not detrimental to cell growth. HCV IRES-mediated cap-independent translation was markedly inhibited in cells constitutively expressing IRNA compared to control hepatoma cells. However, cap-dependent translation was not significantly affected in these cell lines. Additionally, Huh-7 cells constitutively expressing IRNA became refractory to infection by a PV-HCV chimera in which the PV IRES is replaced by the HCV IRES. In contrast, replication of a PV-encephalomyocarditis virus (EMCV) chimera containing the EMCV IRES element was not affected significantly in the IRNA-producing cell line. Finally, the binding of the La autoantigen to the HCV IRES element was specifically and efficiently competed by IRNA. These results provide a basis for development of novel drugs effective against HCV infection.     

Optimized electrostatic surfaces parallel increased thermostability: a structural bioinformatic analysis

It has been known for some time that thermophilic proteins generallyhave increased numbers of non-covalent interactions (salt bridges,hydrogen bonds, etc.) compared with their mesophilic orthologs.Recently, anecdotal structural comparisons suggest that non-specificacid–base ion pairs on the protein surface can be an evolutionaryefficient mechanism to increase thermostability. In this comprehensivestructural analysis, we confirm this to be the case. Comparisonof 127 orthologous mesophilic– thermophilic protein groupsindicates a clear preference for stabilizing acid–basepairs on the surface of thermophilic proteins. Compared withpositions in the core, stabilizing surface mutations are lesslikely to disrupt the tertiary structure, and thus more likelyto be evolutionarily selected. Therefore, we believe that ourresults, in addition to being theoretically interesting, willfacilitate identification of charge-altering mutations likelyto increase the stability of a particular protein structure. Received July 23, 2003; revised October 14, 2003; accepted October 21, 2003     

New Preparation and Purification Methods for Metallo-Supramolecular Block Copolymers

The bis-complex formation of two terpyridine-modified polymers using microwave assisted reaction conditions was investigated in detail. In order to construct a heteroleptic block copolymer polystyrene, which was prepared by nitroxide-mediated radical polymerization (NMRP), and a commercial available poly(ethylene oxide) were used. These studies include the influence of temperature, reaction time, concentration and the use of different solvent mixtures on complexation. The conversion was determined by GPC measurements. The amphiphilic metallo-supramolecular block copolymers were investigated towards their formation of micellar aggregates in water. Other characterization techniques include ¹H-NMR, UV/vis spectroscopy, dynamic light scattering (DLS), atomic force spectroscopy (AFM) and transmission electron microscopy (TEM) techniques. This paper is dedicated to Professor Ian Manners for his scientific contributions to inorganic and organometallic polymers.     

Pulsed-thermal processing of chemically synthesized FePt nanoparticles

The disordered face-centered-cubic A1 to the chemical ordered face-centered-tetragonal L1₀ phase transformation of chemically synthesized magnetic FePt nanoparticles has been studied in the millisecond regime using a pulsed high-density plasma arc light source. Under select annealing conditions, relatively high magnetic coercivities (Hc) and anisotropies (Hk) of FePt nanoparticles were obtained with the millisecond pulse processing without significant sintering of the nanoparticles.     

Connexin 32 gap junctions enhance stimulation of glucose output by glucagon and noradrenaline in mouse liver

Gap junctions connect neighboring cells via intercellular channels composed of connexins (Cx). Connexin 32 (Cx32) is the main connexin in hepatocytes. Gap junctions propagate a signal from periportal to perivenous hepatocytes generated by electrical stimulation of sympathetic liver nerves. Therefore, it was the aim of this study to examine the involvement of hepatocellular gap junctions in hormonal regulation. In perfused livers from wild-type mice and Cx32-deficient mice, the stimulation of glucose release by varying noradrenaline and glucagon concentrations was investigated. At saturating hormone concentrations, glucose release was the same in wild-type and Cx32-deficient livers. However, glucose output was significantly smaller in Cx32-deficient than wild-type livers at half-maximally effective hormone concentrations. Because the two hormones circulate at less than half-saturating concentrations and because they are degraded during passage of blood through the liver, they lose efficiency from the periportal to the perivenous zone. In wild-type livers, this decrease in efficiency can be partially compensated by intercellular signal propagation through gap junctions, resulting in higher hormone actions than in Cx32-deficient livers. It is concluded that gap junctions are not only involved in intercellular propagation of nervous, but also of hormonal signals from periportal to perivenous hepatocytes.     

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population

The noncompetitive N-methyl-D-aspartate (NMDA) antagonists dizocilpine and phencyclidine cause behavioral changes in animals that can be blocked by antipsychotic agents, implicating NMDA receptors in the expression of schizophrenic symptoms. In the present study, we examined the effects of dizocilpine (0.1-3.0 mg/kg s.c.) on locomotor activity and on the expression of c-fos and hsp-70 immediate-early genes (IEGs) in mice. Results indicate that dizocilpine increases locomotor activity and selectively increases the expression of c-fos and hsp-70 in the posterior cingulate cortex. Haloperidol (0.01-0.1 mg/kg) and clozapine (0.6-1.25 mg/kg) block both the locomotor response and the increased IEG immunoreactivity induced by dizocilpine (0.6 mg/kg). The 5-HT2 antagonists ritanserin (0.06-0.25 mg/kg), ketanserin (0.03-0.12 mg/kg) and amesergide (0. 3-1.25 mg/kg) also significantly attenuated the locomotor response to dizocilpine. Haloperidol and clozapine suppressed the head weaving induced by dizocilpine, but ritanserin, as previously reported did not. Although some attenuation of the c-fos and hsp-70 immunoreactivity was seen with the 5-HT2 antagonists it was less pronounced than that induced by haloperidol or clozapine. In conclusion, 5-HT2 antagonists as well as antipsychotic compounds attenuate the locomotor response to dizocilpine in mice. Haloperidol and clozapine appear to be more effective, however, in attenuating the expression of c-fos and hsp-70 in the posterior cingulate gyrus than 5-HT2 antagonists ritanserin, ketanserin or amesergide. We thus have seen a dissociation in the capacity of compounds to alter the effects on behavior and IEG expression after dizocilpine administration.     

On the nature of virtuous change in cultural landscapes: Exploring sustainability through qualitative models

Cultural landscapes are internationally valued resources, yet face endemic threats. Often the 'drivers for change' result in a loss of valued qualities, and are associated with 'vicious circles' of landscape deterioration. The way in which landscape may represent an integrative framework for research and policy is noted. It is argued that a key objective of research and policy should be to promote 'virtuous circles' in which social capital and economic entrepreneurship valorize distinctive landscape characteristics, leading to a situation of mutual reinforcement between human activity and environmental capital. Particular attention is given to qualitative models of virtuosity in the landscape. Positive feedback loops in the landscape are illustrated by reference to current examples of integrated rural projects. The further development of formal models as a basis for reinstating virtuous circles is advocated as a basis for the future planning and understanding of cultural landscapes.     

Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism

Feglymycin, a peptide antibiotic produced by Streptomyces sp. DSM 11171, consists mostly of nonproteinogenic phenylglycine‐type amino acids. It possesses antibacterial activity against methicillin‐resistant Staphylococcus aureus strains and antiviral activity against HIV. Inhibition of the early steps of bacterial peptidoglycan synthesis indicated a mode of action different from those of other peptide antibiotics. Here we describe the identification and assignment of the feglymycin (feg) biosynthesis gene cluster, which codes for a 13‐module nonribosomal peptide synthetase (NRPS) system. Inactivation of an NRPS gene and supplementation of a hydroxymandelate oxidase mutant with the amino acid l ‐Hpg proved the identity of the feg cluster. Feeding of Hpg‐related unnatural amino acids was not successful. This characterization of the feg cluster is an important step to understanding the biosynthesis of this potent antibacterial peptide.