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.     

Influence of series resistance in oxide parameter extraction data from accelerated tests

Accelerated reliability tests on thin oxide capacitors can be affected by series resistance effects at high stress conditions. The purpose of this work is to point out such problems both with measurements and simulations. It is shown that breakdown electric field is overestimated. Due to the resulting nonuniform stress, charge to breakdown density is underestimated if the test structure layout is not accurately designed. In any case the series resistance effects can have an undesirable impact on the reliability evaluation of thin dielectrics.     

Ascitic fluid analysis in hepatocellular carcinoma

BACKGROUND: Ascites in patients with hepatocellular carcinoma (HCC) is a poorly characterized subgroup of malignancy-related ascites. Not only the underlying liver disease, but also the tumor growth and spread contributes to the ascites formation. The authors differentiated ascites in HCC from other types of ascites. METHODS: The authors analyzed the ascitic fluid of 185 consecutive patients (89 liver cirrhosis, 33 HCC, 31 peritoneal carcinomatosis, 22 liver metastases, 10 spontaneous bacterial peritonitis). RESULTS: Each subgroup showed a typical pattern. Compared with the cirrhotic patients, those with HCC showed a higher frequency of positive cytologic findings (4 of 33 versus 0/89, P < 0.004), elevated fibronectin concentration (10/33 versus 8/89, P < 0.004), and elevated polymorphonuclear cell count (10/33 versus 5/89 P < 0.004). CONCLUSIONS: A significant number of patients with ascites and HCC patients showed signs of peritoneal infiltration with positive cytologic findings and increased concentration of fibronectin. Moreover, neutrocytic ascites without signs of superinfection is relatively common (30%).     

Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours

A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

Crystallization,morphology, structure and thermal behaviour of nylon-6/rubber blends

An experimental study was carried out in order to investigate the morphological, kinetic, structural and thermodynamic properties of nylon-6/rubber (namely ethylene-propylene copolymer (EPM) and ethylene-propylene copolymer functionalized by inserting along its backbone succinic anhydride groups (EPM-g-SA)) blends. The morphology and the overall kinetics of crystallization of the blends strongly depend on the type of copolymer added to nylon and on the blend composition. The EPM-g-SA acts as a nucleating agent for the Ny spherulites and at the same time causes a drastic depression of the overall kinetic rate constant. This decrease is related to the increase of the melt viscosity observed in Ny/EPM-g-SA blends. The crystalline lamella thickness of the Ny phase in the blends is lower than that of pure Ny crystallized at the same T_c suggesting that the presence in the melt of an elastomeric phase disturbs the growth of the Ny crystals. The rubber does not influence the thermal behaviour of the nylon. The results found lead to the conclusion that in the melt nylon-6 is incompatible with both EPM and EPM-g-SA copolymers.     

Novel poly(etheraroyl-co-terephthal) hydrazides with liquid crystalline behaviour

Novel poly(etheraroyl-co-terephthal)hydrazides with liquid crystalline (LC) behaviour, synthesized by solution polycondensation followed by non-solvent coagulation in water, have been characterized by means of Fourier Transform infrared (FT-i.r.), differential scanning calorimetry (DSC) and wide angle X-ray scattering (WAXS) techniques. DSC thermograms and WAXS intensity profiles of as polymerized and coagulated homo- and copolymers are strongly dependent upon the molecular structure and constitution of the polymers: the poly(etheraroyl-hydrazide) homopolymer shows an LC behaviour and such a characteristic is maintained in copolymers with low content of terephthaloyldichloride comonomer, while a further increase in comonomer content attenuates this LC attitude. Annealing treatments on as polymerized and coagulated copolymers are able to transform the LC phase metastable at room temperature into crystalline and/or amorphous phases.     

Sensitivity of SAR data to post-fire forest regrowth in Mediterranean and boreal forests

Disturbed forests may need decades to reach a mature stage and optically-based vegetation indices are usually poorly suited for monitoring purposes due to the rapid saturation of the signal with increasing canopy cover. Spaceborne synthetic aperture radar (SAR) data provide an alternate monitoring approach since the backscattered microwave energy is sensitive to the vegetation structure. Images from two regions in Spain and Alaska were used to analyze SAR metrics (cross-polarized backscatter and co-polarized interferometric coherence) from regrowing forests previously affected by fire. TerraSAR-X X-band backscatter showed the lowest sensitivity to forest regrowth, with the average backscatter increasing by 1-2 dB between the most recent fire scar and the unburned forest. Increased sensitivity (around 3-4 dB) was observed for C-band Envisat Advanced Synthetic Aperture (ASAR) backscatter. The Advanced Land Observing Satellite (ALOS) Phased Array-type L-band Synthetic Aperture Radar (PALSAR) L-band backscatter presented the highest dynamic range from unburned to recently burned forests (approximately 8 dB). The interferometric coherence showed low sensitivity to forest regrowth at all SAR frequencies. For Mediterranean forests, five phases of forest regrowth were discerned whereas for boreal forest, up to four different regrowth phases could be discerned with L-band SAR data. In comparison, the Normalized Difference Vegetation Index (NDVI) provided reliable differentiation only for the most recent development stages. The results obtained were consistent in both environments.