A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

La0.6Sr0.4Co0.2Fe0.8O3-δ nanofiber cathode for intermediate-temperature solid oxide fuel cells by water-based sol-gel electrospinning: Synthesis and electrochemical behaviour

Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La_0.6Sr_0.4Co_0.2Fe_0.8O_3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce_0.9Gd_0.1O_1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance R_p is 1.0 Ω cm². Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h.     

Glutamate metabotropic receptor agonists depress excitatory and inhibitory transmission on rat mesencephalic principal neurons

Intracellular and whole-cell patch-clamp recordings were used to evaluate the actions of different metabotropic glutamate receptor (mGluR) agonists on the synaptic inputs evoked on principal cells of the rat mesencephalon. Bath application of the group III mGluR agonists L-2-amino-4-phosphonobutyric acid (L-AP4) and L-serine-O-phosphonobutanoate (L-SOP) did not change the holding current of the cells held at resting potential (-60 mV) but produced a dose-dependent inhibition of the amplitude of the excitatory and inhibitory events. L-AP4 and L-SOP were more effective at inhibiting the excitatory postsynaptic currents (EPSCs) than the GABA(A) and GABA(B) inhibitory postsynaptic currents (IPSCs). The suppressing effects of L-AP4 and L-SOP were antagonized by (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP-4) but not by +/- -alpha-methyl-4-carboxyphenylglycine (MCPG). Moreover, the group II agonist (2S,1'S,2'S)-(carboxycyclopropyl)glycine (L-CCG1) and the group I agonist (RS)-3,5-dihydrophenylglycine (3,5-DHPG) depressed in a dose-related manner the EPSC, the GABA(A) IPSC and the GABA(B) IPSC. The suppressing effect of the two mGluRs agonists was partially antagonized by MCPG but not by MAP-4. In addition, both L-CCG1 and 3,5-DHPG caused an inward shift of the holding current. To characterize the site of action of the metabotropic receptor agonists, experiments were performed to examine the amplitude and ratio of EPSC and GABA(A) IPSC pairs. The increase of the s2/s1 ratio caused by the agonists suggests that the location of the inhibitory mGluRs was presynaptic. These results indicate that the activation of presynaptic mGluRs controls the release of excitatory and inhibitory transmitters on presumed dopaminergic cells within the ventral mesencephalon.     

The effects of growth hormone in children with a GH deficiency: a report of 5 cases

The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone deficiency in prepubertal age, treated with human growth hormone. In four of five cases the response to treatment with GH was relevant. Only in one case (F1) the response was negative. The results of this study confirm that rhGH is a safe and effective therapy in children with GHD.     

Compositional constraints in the extremely GC-poor genome of Plasmodium falciparum

We have analyzed the compositional properties of coding (protein encoding) and non-coding sequences of Plasmodium falciparum, a unicellular parasite characterized by an extremely AT-rich genome. GC% levels, base and dinucleotide frequencies were studied. We found that among the various factors that contribute to the properties of the sequences analyzed, the most relevant are the compositional constraints which operate on the whole genome.     

User modeling in an OAM support system

This paper outlines studies relative to a research project on the development of a system that permits different people of an enterprise, with different roles and experience, to gain an adequate and personalized vision of the real status of the network and managed systems. What has been achieved is an easy to handle system, which permits quick and simple queries without utilizing complex man machine languages, and tailors personalized answers on the basis of the characteristics of the user. To achieve these results, User Modeling aspects have been considered and pursued.