Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules

Cathepsin X is a lysosomal peptidase that is involved in tumour progression and represents a potential target for therapeutic interventions. In addition, it regulates important functions of immune cells and is implicated in the modulation of tumour cell–immune cell crosstalk. Selective cathepsin X inhibitors have been proposed as prospective antitumour agents to prevent cancer progression; however, their impact on the antitumour immune response has been overlooked. Previous studies indicate that the migration and adhesion of T cells and dendritic cells are affected by diminished cathepsin X activity. Meanwhile, the influence of cathepsin X inhibition on natural killer (NK) cell function has not yet been explored. Here, we examined the localization patterns of cathepsin X and the role of its inhibitors on the cytotoxicity of cell line NK-92, which is used for adoptive cellular immunotherapy in cancer patients. NK-92 cells depend on lymphocyte function-associated antigen 1 (LFA-1) to form stable immunoconjugates with target cells, providing, in this way, optimal cytotoxicity. Since LFA-1 is a substrate for cathepsin X activity in other types of cells, we hypothesized that cathepsin X could disturb the formation of NK-92 immunoconjugates. Thus, we employed cathepsin X reversible and irreversible inhibitors and evaluated their effects on the NK-92 cell interactions with target cells and on the NK-92 cell cytotoxicity. We show that cathepsin X inhibition does not impair stable conjugate formation or the lytic activity of NK-92 cells. Similarly, the conjugate formation between Jurkat T cells and target cells was not affected by cathepsin X activity. Unlike in previous migration and adhesion studies on T cells, in NK-92 cells cathepsin X was not co-localized with LFA-1 at the plasma membrane but was, rather, redistributed to the cytotoxic granules and secreted during degranulation.     

Genetic programming hyperheuristic parameter configuration using fitness landscape analysis

Applied Intelligence - Fitness landscape analysis is a tool that can help us gain insight into a problem, determine how hard it is to solve a problem using a given algorithm, choose an algorithm...     

Coagulase-negative staphylococci from non-mastitic bovine mammary gland: characterization of Staphylococcus chromogenes and Staphylococcus haemolyticus by antibiotic susceptibility testing and pulsed-field gel electrophoresis

During routine microbiological examination of milk samples from dairy cows without clinical signs of mastitis, quarter milk samples of 231 dairy cows from 12 herds were investigated for the presence of coagulase-negative staphylococci (CNS). The isolates were identified on the basis of colony morphology, Gram staining, catalase and coagulase test and the commercial kit, API Staph. CNS was detected in 29% (67/231) of the cows. A total of seven CNS species were identified with the most prevalent being Staphylococcus (Staph.) chromogenes (30%) and Staph. haemolyticus (28·8%), followed by Staph. simulans (11·2%), Staph. xylosus (11·2%), Staph. epidermidis (7·5%), Staph. hyicus (6·3%) and Staph. sciuri (5%). The predominant species, Staph. chromogenes and Staph. haemolyticus, were further characterized by antibiotic susceptibility testing using the agar disc diffusion method (Kirby-Bauer) and by pulsed-field gel electrophoresis (PFGE). Considerable resistance to ampicillin and penicillin was observed in both species. Isolates with identical or highly similar PFGE profiles were detected at the herd level despite a marked heterogeneity seen for both species. On the basis of somatic cell count, absence of clinical signs of inflammation and heterogeneity of genotypes, we assume that CNS isolated in this study could not be considered as important causative agents of the bovine mammary gland inflammation.     

Use of regression methods for determining the relation between theoretical–linear and spectrophotometrical colour values of bicolour woven structures

In this paper, new approaches for evaluating the entire colour effect of optical mixing of bicolour woven structures are presented. Simple woven structures with constant colour in the warp direction and different colours in the weft direction were prepared and analysed. The constructional parameters of these woven fabrics were systematically changed, which resulted in the variations of the fractions of colour components and, consequently, also in the changes of colour properties (lightness, hue, chroma) of bicolour optical mixtures. The position of colours of the bicolour structures and the approximate direction (linear) of colour changes in CIELAB colour space were theoretically determined with a simple geometrical model and additive method. Furthermore, the bicolour optical effects were determined spectrophotometrically. The differences between the linear–theoretical and the spectrophotometrical colour values of bicolour woven fabrics were mathematically analysed with linear and non‐linear regression methods to determine the positions of colour coordinates L*, a* and b* of bicolour woven fabrics in the a*b* plane by increasing or reducing the cover factors of warp and weft threads (addition or reduction of colour components). The results present, on the one hand, the strong influence of original colours of warp and weft threads and, on the other hand, the minor influence of constructional parameters on the form of linear/non‐linear behaviour of colours of bicolour compositions. When the characteristics of a specific colour combination are taken into account, the spectrophotometrical colour values of bicolour woven fabrics can be also mathematically determined with additive–theoretical colour values and, to some extent, with predictable colour deviations.     

Cadmium accumulation by muskmelon under salt stress in contaminated organic soil

Human-induced salinization and trace element contamination are widespread and increasing rapidly, but their interactions and environmental consequences are poorly understood. Phytoaccumulation, as the crucial entry pathway for biotoxic Cd into the human foodstuffs, correlates positively with rhizosphere salinity. Hypothesising that organic matter decreases the bioavailable Cd²⁺ pool and therefore restricts its phytoextraction, we assessed the effects of four salinity levels (0, 20, 40 and 60 mM NaCl) and three Cd levels (0.3, 5.5 and 10.4 mg kg^− 1) in peat soil on mineral accumulation/distribution as well as vegetative growth and fruit yield parameters of muskmelon (Cucumis melo L.) in a greenhouse. Salt stress reduced shoot biomass and fruit production, accompanied by increased Na and Cl and decreased K concentration in above-ground tissues. A 25- and 50-day exposure to salinity increased Cd accumulation in leaves up to 87% and 46%, respectively. Accumulation of Cd in the fruits was up to 43 times lower than in leaves and remained unaltered by salinity. Soil contamination by Cd enhanced its accumulation in muskmelon tissues by an order of magnitude compared with non-contaminated control. In the drainage solution, concentrations of Na and Cl slightly exceeded those in the irrigation solution, whereas Cd concentration in drainage solution was lower by 2-3 orders of magnitude than the total amount added. Chemical speciation and distribution modelling (NICA-Donnan) using Visual MINTEQ showed predominance of dissolved organic ligands in Cd chemisorption and complexation in all treatments; however, an increase in salt addition caused a decrease in organic Cd complexes from 99 to 71%, with free Cd²⁺ increasing up to 6% and Cd-chlorocomplexes up to 23%. This work highlights the importance of soil organic reactive surfaces in reducing trace element bioavailability and phytoaccumulation. Chloride salinity increased Cd accumulation in leaves but not in fruit peel and pulp.     

Learning Strategies for Mechanised Building of Decision Procedures

In this paper we present an investigation into whether and how decision procedures can be learnt and built automatically. Our approach consists of two stages. First, a refined brute-force search procedure applies exhaustively a set of given elementary methods to try to solve a corpus of conjectures generated by a stochastic context-free grammar. The successful proof traces are saved. In the second stage, a learning algorithm (by Jamnik et al.) tries to extract a required supermethod (i.e., decision procedure) from the given traces. In the paper, this technique is applied to elementary methods that encode the operations of the Fourier-Motzkin's decision procedure for Presburger arithmetic on rational numbers. The results of our experiment are encouraging.     

Lipase-catalyzed esterification of citronellol with lauric acid in supercritical carbon dioxide/co-solvent media

Direct esterification of citronellol and lauric acid catalyzed by immobilized lipase B from Candida antarctica was performed in supercritical carbon dioxide with different organic solvents and ionic liquids serving as co-solvents. The highest concentration of citronellol laurate after 1 h of reaction performance (3.95 mmol/g substrates) was obtained in SC CO₂ with ethyl methylketone serving as a co-solvent. The optimal temperature and pressure for citronellol laurate synthesis in SC CO₂/EMK medium was determined to be 60 °C and 10 MPa.     

What Makes an Effective Representation of Information: A Formal Account of Observational Advantages

In order to effectively communicate information, the choice of representation is important. Ideally, a chosen representation will aid readers in making desired inferences. In this paper, we develop the theory of observation: what it means for one statement to be observable from another. Using observability, we give a formal characterization of the observational advantages of one representation of information over another. By considering observational advantages, people will be able to make better informed choices of representations of information. To demonstrate the benefit of observation and observational advantages, we apply these concepts to set theory and Euler diagrams. In particular, we can show that Euler diagrams have significant observational advantages over set theory. This formally justifies Larkin and Simon’s claim that “a diagram is (sometimes) worth ten thousand words”.     

How much do cultivar and preparation time influence on phenolics content in walnut liqueur?

The influence of cultivar and picking date on the phenolic content of walnut liqueur was investigated using HPLC with a PDA detector. Ten phenolic compounds, namely gallic, protocatechuic, ellagic, chlorogenic (5-caffeoylquinic), syringic, p-coumaric and sinapic acids, as well as (+)-catechin, 1,4-naphthoquinone and juglone were detected. The walnut liqueur under analysis was made of the cultivars ‘Franquette’ and ‘Elit’, on two sampling dates (June 30th and July 7th). A close interaction between cultivar and sampling date was noticed for most of the phenolics analyzed. The content levels of the main phenolic compounds under investigation were highest in ‘Franquette’ at the end of June and lowest in ‘Elit’ on the second or both sampling dates, except for syringic acid. A strong influence of cultivar choice and picking date was observed. The content levels of most phenolics were higher in liqueur prepared from the cultivar ‘Franquette’, than in ‘Elit’.     

Phenolic compounds in some apple (Malus domestica Borkh) cultivars of organic and integrated production

Eleven organically grown apple cultivars and 11 apple cultivars of integrated production from Austria and Slovenia were analyzed by HPLC for the content of phenolic compounds in peel and pulp. We identified chlorogenic acid, p‐coumaric acid, procyanidin B3, protocatechuic acid, (?)‐epicatechin, phloridzin, rutin and quercetin‐3‐rhamnoside in apple peel. In apple pulp, (+)‐catechin was also identified in all the cultivars. Some other phenols (procyanidin B3, rutin and quercetin‐3‐rhamnoside) could not be identified or were not properly separated. With regard to the phenolic content in the apple peel, there were no differences between organically grown apple cultivars and apple cultivars of integrated production. Organically grown apples, however, exhibited a higher content of phenolic substances in the apple pulp compared with the apple cultivars of integrated production. This may be due either to the different genotype source or to the growing technology. Higher concentrations of phenolic compounds in organically grown cultivars could be a result of plant response to stress. The apple peel contained higher concentrations of identified phenols than the pulp. The apple peel represents up to 10% of the whole fruit; therefore the phenolsic compounds in the pulp are of greater importance to the consumer than the phenolic compounds in the peel. Copyright © 2005 Society of Chemical Industry