Fibroblast surface antigen (SF): Molecular properties,distribution in vitro and in vivo,and altered expression in transformed cells

We have recently described a cell type-specific surface (SF) antigen that is deleted in chick fibroblasts transformed by Rous sarcoma virus. SF antigen is a major surface component and makes up about 0.5% of the total protein on normal cultured fibroblasts. The antigen is shed from normal cells and is present in circulation (serum, plasma), and in vivo, also, in tissue boundary membranes. The molecular equivalents of both cellular and serum SF antigen are distinct, large polypeptides, one of which (SF210, MW 210,000) is glycosylated and, on the cell surface, highly susceptible to proteases and accessible to surface iodination. Immunofluorescence and scanning electron microscopy have indicated that the antigen is located in fibrillar structures of the cell surface, membrane ridges, and processes. Human SF antigen is present in human fibroblasts and in human serum. We have recently shown that human SF antigen is identical to what has been known as the “cold-insoluble globulin” and that it shows affinity toward fibrin and fibrinogen. Our results also indicate that loss of the transformation-sensitive surface proteins is due not to loss of synthesis but to lack of insertion of the protein in the neoplastic cell surface. Both normal and transformed cells produce the SF antigen, but the latter do not retain it in the cell surface. The loss of SF antigen, a major cell surface component, from malignant cells creates an impressive difference between the surface properties of normal and malignant cells. The possible significance of SF antigen to the integrity of the normal membrane and its interaction to surrounding structures is discussed.     

Toxic and non-toxic Nodularia strains can be distinguished from each other and from eukaryotic algae with chlorophyll fluorescence fingerprinting

Chlorophyll fluorescence induction curves of toxic and non-toxic strains of the cyanobacterium Nodularia were measured and compared with fluorescence curves measured from four species of eukaryotic algae. Both cyanobacteria and algae were isolated from the Baltic Sea. The results show that Nodularia strains can be distinguished from the eukaryotes by applying a pattern recognition procedure to the fluorescence induction curves, suggesting that the fluorescence fingerprinting technique might be useful in environmental monitoring of marine algae. The six studied Nodularia strains could not be distinguished from each other from their fluorescence induction kinetics. However, their fluorescence curves fell into two clear categories, the toxic and the non-toxic Nodularia. Emission spectroscopy and differences in the fluorescence induction curves showed that the ratio of the intensity of the Photosystem I emission peak to the Photosystem II peak is higher in non-toxic Nodularia than in the toxic strains, suggesting that the toxicity affects the structure of the photosynthesis machinery. The effect on photosynthesis may be related to the ability of the microcystins to chelate iron.     

Immune responses to Puumala virus infection and the pathogenesis of nephropathia epidemica

Puumala virus, causative agent of a mild form of hemorrhagic fever with renal syndrome, also known as nephropathia epidemica, induces long-lasting humoral and cellular immunity in patients. The virus itself is not cytopathic, and the immune responses to the virus may be involved in teh pathogenesis of the disease.     

How Close Do We Live to Water? A Global Analysis of Population Distance to Freshwater Bodies

Traditionally, people have inhabited places with ready access to fresh water. Today, over 50% of the global population lives in urban areas, and water can be directed via tens of kilometres of pipelines. Still, however, a large part of the world''s population is directly dependent on access to natural freshwater sources. So how are inhabited places related to the location of freshwater bodies today? We present a high-resolution global analysis of how close present-day populations live to surface freshwater. We aim to increase the understanding of the relationship between inhabited places, distance to surface freshwater bodies, and climatic characteristics in different climate zones and administrative regions. Our results show that over 50% of the world''s population lives closer than 3 km to a surface freshwater body, and only 10% of the population lives further than 10 km away. There are, however, remarkable differences between administrative regions and climatic zones. Populations in Australia, Asia, and Europe live closest to water. Although populations in arid zones live furthest away from freshwater bodies in absolute terms, relatively speaking they live closest to water considering the limited number of freshwater bodies in those areas. Population distributions in arid zones show statistically significant relationships with a combination of climatic factors and distance to water, whilst in other zones there is no statistically significant relationship with distance to water. Global studies on development and climate adaptation can benefit from an improved understanding of these relationships between human populations and the distance to fresh water.     

Nitrogen Requirement of Iron-Oxidizing Thiobacilli for Acidic Ferric Sulfate Regeneration

Ammonium was shown to be a limiting nutrient for iron oxidation in cultures of Thiobacillus ferrooxidans. In addition, one strain was also able to assimilate nitrate, but not nitrite, for growth and coupled iron oxidation. Some amino acids (0.5 mM) were tested as a source of nitrogen; none clearly stimulated bacterial activity and inhibition was commonly encountered. Complex nitrogenous compounds were inhibitory at high concentrations (0.1 to 0.5%, wt/vol) and, at low concentrations, some clearly stimulated the bacterial iron oxidation in ammonium-limited cultures. Enhancement of iron oxidation by these compounds was also observed in ammonium-unlimited cultures, suggesting their possible role in providing trace nutrients and possibly carbon for the bacteria.     

Conformation study of 2-arylbenzimidazoles as inhibitors of Chlamydia pneumoniae growth

Chlamydia pneumoniae is a worldwide cause of various respiratory track diseases ranging from asymptomatic pharyngeal infection to severe, sometimes fatal pneumonia. We have previously identified 2-arylbenzimidazoles as highly active antichlamydial compounds. In this work the importance of conformational effects on the structure-activity relationship of these compounds was studied. To simplify calculations, properly substituted N-phenylbenzamides, or the corresponding heterocyclic compounds, and 2-arylbenzimidazoles were used as model compounds. They were energy minimized and the energy differences between certain conformations were calculated. The main finding was that the compounds which can more easily adopt a non-planar conformation show higher bioactivity. This finding can be utilized in designing new derivatives or in constructing a pharmacophore model.     

Stochastic boundary molecular dynamics simulation of L-ribose in the active site of Actinoplanes missouriensis xylose isomerase and its Val135Asn mutant with improved reaction rate

We used molecular dynamics simulations to study how a non-natural substrate, L-ribose, interacts with the active site of Actinoplanes missouriensis xylose isomerase. The simulations showed that L-ribose does not stay liganded in the active site in the same way as D-xylose, in which the oxygens O2 and O4 are liganded to the metal M1. The oxygen O4 of L-ribose moved away from the metal M1 to an upside down position. Furthermore, the distances of the carbons C1 and C2 of L-ribose to the catalytic metal M2 were higher than in the case of D-xylose. These findings explain the extremely low reaction rate of xylose isomerase with L-ribose. The mutation V135N close to the C5-OH of the substrate increased the reaction efficiency 2- to 4-fold with L-ribose. V135N did not affect the reaction with D-xylose and L-arabinose, whereas the reaction with D-glucose was impaired, probably due to a hydrogen bond between Asn-135 and the substrate. When L-ribose was the substrate, Asn-135 formed a hydrogen bond to Glu-181. As a consequence, O4 of L-ribose stayed liganded to the metal M1 in the V135N mutant in molecular dynamics simulations. This explains the decreased K(m) of the V135N mutant with L-ribose.     

Ring-cleaving cyanuric acid amidohydrolase activity in the atrazine-mineralizing Ralstonia basilensis M91-3

The purpose of this study was to characterize the cyanuric acid amidohydrolase reaction in Ralstonia basilensis M91-3, an atrazine-mineralizing soil bacterium. This ring fission reaction is the last aromatic step in the degradative pathway of atrazine and other s-triazines. The products and molar stoichiometry of the cyanuric acid amidohydrolase reaction were one mol biuret (H₂N·CO·NH·CO·NH₂) and one mol CO₂ per mol cyanuric acid hydrolyzed, as confirmed by ¹³C-NMR and gas chromatography. The optimum pH and temperature, substrate specificity, and kinetic parameters were also characterized for the purified enzyme. The native enzyme had two forms of different sizes, 204 kDa and 160 kDa. Each was a tetramer or pentamer of 44 kDa and 33 kDa, respectively.