Virtual Screening against p50 NF‐κB Transcription Factor for the Identification of Inhibitors of the NF‐κB–DNA Interaction and Expression of NF‐κB Upregulated Genes

Virtual screening against NF‐κB p50 using docking simulations was applied by starting from a three‐dimensional (3D) database containing more than 4.6 million commercially available structures. This database was filtered by specifying a subset of commercially available compounds sharing a (2E,Z)‐3‐(2‐hydroxyphenyl)‐2‐propenoate substructure and relevant druglike properties. Docking to p50 NF‐κB was performed with a test set of six known inhibitors of NF‐κB–DNA interactions. In agreement with docking results, the highest‐scored compound displayed a high level of inhibitory activity in electrophoretic mobility shift assay (EMSA) experiments (inhibition of NF‐κB–DNA interactions) and on biological functions dependent on NF‐κB activity (inhibition of IL‐8 gene expression in cystic fibrosis IB3‐1 cells). We found that this in silico screening approach is suitable for the identification of low‐molecular‐weight compounds that inhibit NF‐κB–DNA interactions and NF‐κB‐dependent functions. Information deduced from the discovery of the new lead compound and its binding mode could result in further lead optimization resulting in more potent NF‐κB inhibitors.     

Silver nanocluster–silica composite coatings with antibacterial properties

Silver nanocluster–silica composite coatings have been deposited by radio frequency (RF) co-sputtering on silica substrates. UV–visible absorption and X-ray diffraction spectra of the as deposited and heated samples revealed metal silver nanoclusters of different size, depending on the annealing treatment. The antibacterial activity of several as deposited and annealed samples has been verified in accordance to National Committee for Clinical Laboratory Standards (NCCLS). The antibacterial activity of these coatings was detected up to 450 °C.     

Intestinal obstruction caused by phytobezoar: computerized tomography findings. Report of 3 cases

Fc gammaRIII (CD16) expression on the surfaces of polymorphonuclear neutrophils was significantly reduced in human immunodeficiency virus type 1-seropositive patients with pulmonary tuberculosis compared to that in individuals with either disease alone or in healthy blood donors. This downregulation of Fc gammaRIII may contribute to the enhanced susceptibility of coinfected individuals to opportunistic infections.     

Epidemiology and alcoholism among worker populations

In summary, seventeen infertile men with varicocele in whom no other cause for infertility could be identified, were studied before and following varicocele repair. Morphologic alterations were the most common abnormality noted in the seminal fluid with all subjects demonstrating increased numbers of tapered or amorphous spermatozoa. Ligation of the varicocele resulted in improvement in one or more of the seminal fluid abnormalities in thirteen of the seventeen patients. Seven patients achieved a pregnancy. No single seminal fluid parameter was identified which was of predictive value in determining those subjects who would demonstrate improvement following varicocele repair.     

A Spectroscopic Study of Group IV Transition-Metal-Incorporated Direct Templated Mesoporous Catalysts. Part 2. A Comparison of Ti-, Zr- and Hf-Containing Materials

Ti, Zr and Hf ions have been incorporated into mesoporous silica using a novel one-pot procedure based on the true liquid crystal templating (TLCT) synthesis method. The nature of the metallic sites was assessed using diffuse reflectance UV-visible, photoluminescence and FT-IR spectroscopy. In situ adsorption of oxygen and ammonia probe molecules provided information on the accessibility of optically active species.     

Platelet/polymorphonuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a signaling molecule

Polymorphonuclear leukocyte (PMN) adhesion to activated platelets is important for the recruitment of PMN at sites of vascular damage and thrombus formation. We have recently shown that binding of activated platelets to PMN in mixed cell suspensions under shear involves P-selectin and the activated beta2-integrin CD11b/CD18. Integrin activation required signaling mechanisms that were sensitive to tyrosine kinase inhibitors.1 Here we show that mixing activated, paraformaldehyde (PFA)-fixed platelets with PMNs under shear conditions leads to rapid and fully reversible tyrosine phosphorylation of a prominent protein of 110 kD (P approximately 110). Phosphorylation was both Ca2+ and Mg2+ dependent and was blocked by antibodies against P-selectin or CD11b/CD18, suggesting that both adhesion molecules need to engage with their respective ligands to trigger phosphorylation of P approximately 110. The inhibition of P approximately 110 phosphorylation by tyrosine kinase inhibitors correlates with the inhibition of platelet/PMN aggregation. Similar effects were observed when platelets were substituted by P-selectin-transfected Chinese hamster ovary (CHO-P) cells or when PMN were stimulated with P-selectin-IgG fusion protein. CHO-P/PMN mixed-cell aggregation and P-selectin-IgG-triggered PMN/PMN aggregation as well as P approximately 110 phosphorylation were all blocked by antibodies against P-selectin or CD18. In each case PMN adhesion was sensitive to the tyrosine kinase inhibitor genistein. The antibody PL-1 against P-selectin glycoprotein ligand-1 (PSGL-1) blocked platelet/PMN aggregation, indicating that PSGL-1 was the major tethering ligand for P-selectin in this experimental system. Moreover, engagement of PSGL-1 with a nonadhesion blocking antibody triggered beta2-integrin-dependent genistein-sensitive aggregation as well as tyrosine phosphorylation in PMN. This study shows that binding of P-selectin to PSGL-1 triggers tyrosine kinase-dependent mechanisms that lead to CD11b/CD18 activation in PMN. The availability of the beta2-integrin to engage with its ligands on the neighboring cells is necessary for the tyrosine phosphorylation of P approximately 110.     

Microgravity simulation: physical and psychological workload evaluation tests in an underwater environment

As weightlessness is not completely reproducible on Earth, usability evaluation of space systems is often simulated through tests in an aquatic environment. A Neutral Buoyancy Facility test programme was organized in a special pool to simulate Extra-Vehicular Activities on the Columbus module of the future International Space Station with the aim of assessing various aspects of crew interface design.This study was designed to evaluate workload using visibility, accessibility and operability tests. Diving workload was determined through basic physiological measurements, such as pulmonary ventilation and heart rate during underwater operations.As anxiety can influence physiological processes, and consequently also the workload evaluation determined through these parameters, we developed an evaluation methodology to investigate the anxiety level based on a specific questionnaire submitted to all subjects before and after the dives.Heart rate increased in underwater work to a value approximately 50% larger than the value obtained in the resting condition while sitting outside the pool. This increase in heart rate was accompanied by an increase in pulmonary ventilation of 200% larger than the value recorded in the rest condition while sitting outside the water. The extent of these increases was notable in all the test subjects, who varied in age and stature.Recorded values of workload, heart rate and pulmonary ventilation were evaluated on the basis of Christensen's (Arbeitsphysiol. 14 (1950) 251) and Wells’ (J. Appl. Physiol. 10 (1957) 51) classifications. Through this analysis it was possible to determine that the workload, indicated by performance on our neutral buoyancy tests, corresponds to moderate physiological work.For test subjects, anxiety related to underwater performance was light. Among the causes of anxiety all the subjects indicated the lack of confidence with neutral buoyancy tests and a feeling of lack of safety, typical of aquatic environments.We can conclude that context did not produce considerable psychological effects, and consequently that the psychological load did not influence heart rate and pulmonary ventilation values that can therefore be directly related to task workload.     

Mapping salt-marsh vegetation by multispectral and hyperspectral remote sensing

Tidal marshes are characterized by complex patterns both in their geomorphic and ecological features. Such patterns arise through the elaboration of a network structure driven by the tidal forcing and through the interaction between hydrodynamical, geophysical and ecological components (chiefly vegetation). Intertidal morphological and ecological structures possess characteristic extent (order of kilometers) and small-scale features (down to tens of centimeters) which are not simultaneously accessible through field observations, thus making remote sensing a necessary observation tool. This paper describes a set of remote sensing observations from several satellite and airborne platforms, the collection of concurrent ground reference data and the vegetation distributions that may be inferred from them, with specific application to the Lagoon of Venice (Italy). The data set comprises ROSIS, CASI, MIVIS, IKONOS and QuickBird acquisitions, which cover a wide range of spatial and spectral resolutions. We show that spatially-detailed and quantitatively reliable vegetation maps may be derived from remote sensing in tidal environments through unsupervised (K-means) and supervised algorithms (Maximum Likelihood and Spectral Angle Mapper). We find that, for the objective of intertidal vegetation classification, hyperspectral data contain largely redundant information. This in particular implies that a reduction of the spectral features is required for the application of the Maximum Likelihood classifier. A large number of experiments with different feature extraction/selection algorithms show that the use of four bands derived from Maximum Noise Fraction transforms and four RGBI broad bands obtained by spectral averaging yield very similar classification performances. The classifications from hyperspectral data are somewhat superior to those from multispectral data, but the close performance and the results of the features reduction experiments show that spatial resolution affects classification accuracy much more importantly than spectral resolution. Monitoring schemes of tidal environment vegetation may thus be based on high-resolution satellite acquisitions accompanied by systematic ancillary field observations at a relatively limited number of reference sites, with practical consequences of some relevance.     

Pronase-immobilized enzyme reactor: an approach for automation in glycoprotein analysis by LC/LC-ESI/MSn

An automated analytical approach is proposed for simultaneous characterization of glycan and peptide moieties in pronase-generated glycopeptides. The proposed method is based on the use of a new pronase-immobilized enzyme reactor for the on-line rapid digestion of the target glycoprotein. By coupling the bioreactor to a Hypercarb chromatographic trap column, on-line selective glycopeptide enrichment prior to normal-phase liquid chromatography-mass spectrometry was obtained. A detailed study was carried out for integration and automation of each phase of the proposed analytical procedure. On-line digestion allowed extensive cleavage of the model protein (ribonuclease B), yielding to glycopeptides with peptide moieties up to eight amino acids, carrying the Man5-Man9 N-glycans each, selectively resolved on an Amide-80 column. The use of a linear ion trap instrument resulted in efficient ion capture and led to MS3 acquisition times and spectra quality similar to those for MS2, allowing the unambiguous identification of glycan (MS2) and peptide (MS3) sequences. The proposed procedure reduces the glycoprotein analysis time from approximately 3 days, as in most of the traditional off-line methods, to approximately 1 h.