Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression/metastasis. In this study, we have assessed the role of IL-1 and IL-17 in the control of antitumor immunity versus progression in a model of experimental lung metastasis, using 3LL and B16 epithelial tumor cells. The absence of IL-1 signaling or its excess in the lung microenvironment (in IL-1β and IL-1R antagonist knockout [KO] mice, respectively) resulted in a poor prognosis and reduced T cell activity, compared with WT mice. In IL-1β KO mice, enhanced T regulatory cell development/function, due to a favorable in situ cytokine network and impairment in APC maturation, resulted in suppressed antitumor immunity, whereas in IL-1R antagonist KO mice, enhanced accumulation and activity of myeloid-derived suppressor cells were found. Reduced tumor progression along with improved T cell function was found in IL-17 KO mice, compared with WT mice. In the microenvironment of lung tumors, IL-1 induces IL-17 through recruitment of γ/δ T cells and their activation for IL-17 production, with no involvement of Th17 cells. These interactions were specific to the microenvironment of lung tumors, as in intrafootpad tumors in IL-1/IL-17 KO mice, different patterns of invasiveness were observed and no IL-17 could be locally detected. The results highlight the critical and unique role of IL-1, and cytokines induced by it such as IL-17, in determining the balance between inflammation and antitumor immunity in specific tumor microenvironments. Also, we suggest that intervention in IL-1/IL-17 production could be therapeutically used to tilt this balance toward enhanced antitumor immunity.     

Control of K+ influx in 3T3 cells transformed by a conditional mutant of Rous sarcoma virus

Mouse 3T3 cells transformed by a conditional mutant of Rous sarcoma virus (LA90) can assume either a normal or a transformed phenotype, depending on the temperature of cultivation. These cells (LA90) were arrested at the G0/G1 phase of the cell cycle by starvation for serum growth factors at the nonpermissive temperature (39 degrees C). Release from the G0/G1 phase by serum growth factors resulted in a rapid stimulation of Rb+ influx. To investigate whether the stimulation of Rb+ influx is obligatory for cell proliferation, the cultures were released from the G0/G1 phase by a temperature decrease in the absence of serum. A temperature decrease from 39 to 32 degrees C activated the viral pp60src gene mitogenic activity. Under these conditions, no rapid stimulation of Rb+ influx was observed. These results suggest that the rapid stimulation of Rb+ influx induced by serum growth factors is not an essential signal for cell release from the G0/G1 phase. However, a delayed increase in Rb+ influx concomitant with an increase in the cell content of K+ was observed in the cultures released from the G0/G1 phase by temperature decrease in the absence of serum growth factors. We found that the LA90 cells incubated at the permissive temperature (32 degrees C) secreted a mitogenic activity into the medium. Moreover, the conditioned medium from cultures incubated at 32 degrees C, but not at 39 degrees C, stimulate Rb+ influx in G0/G1 cells. These results indicate that Rous sarcoma virus pp60src induces a slow autocrine secretion of a mitogenic activity. This mitogenic activity slowly modulates the K+ content. Therefore, the slow elevation in cellular content of K+ is proposed to be an obligatory event for proliferation in normal and transformed cells.     

Maximum-entropy decomposition of fluorescence correlation spectroscopy data: application to liposome–human serum albumin association

Fluorescence correlation spectroscopy was used to measure the diffusion behavior of a mixture of DMPC or DMPC/DMPG liposomes with human serum albumin (HSA) and mesoporphyrin (MP), which was used as the fluorescent label for liposomes and HSA as well. For decomposing the fluorescence intensity autocorrelation function (ACF) into components corresponding to a liposome population, HSA and MP, we used a maximum entropy procedure that computes a distribution of diffusion times consistent with the ACF data. We found that a simple parametric non-linear fit with a discrete set of decay components did not converge to a stable parameter set. The distribution calculated with the maximum entropy method was stable and the average size of the particles calculated from the effective diffusion time was in good agreement with the data determined using the discrete-component fit.     

A Paecilomyces fumosoroseus mutant over-producing chitinase displays enhanced virulence against Bemisia tabaci

A Paecilomyces fumosoroseus strain was mutagenized by u.v. Among 200 colonies, one mutant (M84), showed a large and stable chitin hydrolysis-halo. Glucose consumption and biomass production were similar for M84 and the parental strain. Chitinase was inducible by chitin and repressed by glucose in both strains but, when they were grown on minimal medium plus colloidal chitin as sole carbon source, the parental and M84 strains yielded 198 and 690 mol N-acetylglucosamine, respectively. This results indicate that the mutant strain synthesized a chitinase with a higher activity. Bioassays against Bemisia tabaci nymph, showed that M84 incited a 2-fold higher incidence of disease compared to the parental strain.     

Airborne pollen sampling in Toledo, Central Spain

Toledo is one of the main tourist spots of Spain, attracting around two million visitors per year. Its geographical situation in the vast and scarcely monitored Region of Castilla La Mancha and the high number of tourists (especially in the spring) has resulted in the Spanish Aerobiology Network (REA) making this city a major study objective. Air monitoring studies carried out using REA sampling procedures commenced in October 2002. Thirty-two pollen types were identified during the sampling period (October 2002 to October 2004). The annual Pollen Index (PI) was 44124 for the agricultural year October 2002–October 2003, and 29666 in the same period of 2003–2004. The most abundant taxa were, in decreasing order of dominance: Cupressaceae, Quercus, Poaceae, Populus, Olea, Urticaceae, Platanus, Pinus and Ulmus. Other, less well-represented pollen taxa included Salix, Alnus, Fraxinus and Tamarix, which were characteristic of riverside areas, and Morus, Artemisia and Chenopodiaceae. The presence of Castanea pollen grains originating from chestnut crops far away from the city was clearly an example of long-distance transport. The highest concentrations of airborne pollen were detected from March to May and also in January, due to the flowering of Cupressaceae species. In general, there was a correlation between pollen and meteorological parameters: a positive correlation with temperature and a negative correlation with rainfall and humidity during the pre-peak period. A negative correlation between temperature and some tree pollen taxa was detected in the principal pollen period correlation analysis due to their long pollination periods.     

Ecology of <Emphasis Type="Italic">Scedosporium</Emphasis> Species: Present Knowledge and Future Research

The genus Scedosporium, which comprises at least five clinically relevant species, i.e. Scedosporium apiospermum, Scedosporium boydii, Scedosporium aurantiacum, Scedosporium dehoogii and Scedosporium minutisporum, ranks the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). This colonization of the airways is thought to contribute to the inflammatory reaction leading to a progressive deterioration of the lung function. Additionally, these colonizing fungi may lead to severe disseminated infections in case of lung transplantation. Therefore, considering the low susceptibility of Scedosporium species to all current antifungal drugs, preventive measures should be defined to reduce the risk of exposure to these fungi for non-colonized CF patients. With this in mind, several studies have been conducted to elucidate the ecology of these fungi and to define possible sources of patient contamination. This review will summarize the major outcomes of those studies, including: the clear demonstration that ecological niches of Scedosporium species are strongly impacted by human activities, and the ability of Scedosporium species to degrade aliphatic and aromatic pollutants which supports the high occurrence of these species in contaminated soils and polluted waters and makes them promising candidates for bioremediation purposes. Finally, prospects for future research in this field are proposed.     

Aerobic biodegradation of a mixture of sulfonated azo dyes by a bacterial consortium immobilized in a two‐stage sparged packed‐bed biofilm reactor

The biodegradation of the sulfonated azo dyes, Acid Orange 7 (AO7) and Acid Red 88 (AR88), by a bacterial consortium isolated from water and soil samples obtained from sites receiving discharges from textile industries, was evaluated. For a better removal of azo dyes and their biodegradation byproducts, an aerobically operated two‐stage rectangular packed‐bed biofilm reactor (2S‐RPBR) was constructed. Because the consortium's metabolic activity is affected by oxygen, the effect of the interstitial air flow rate Q_GI on 2S‐RPBR's zonal values of the oxygen mass transfer coefficient k_La was estimated. In the operational conditions probed in the bioreactor, the k_La values varied from 3 to 60 h^?1, which roughly correspond to volumetric oxygen transfer rates, dc_L/dt, ranging from 20 to 375 mg O₂ L^?1h^?1. Complete biodegradation of azo dyes was attained at loading rates B_V,AZ up to 40 mg L^?1d^?1. At higher B_V,AZ values (80 mg L^?1 d^?1), dye decolorization and biodegradation of the intermediaries 4‐amino‐naphthalenesulphonic acid (4‐ANS) and 1‐amino‐2‐naphthol (1‐A2N) was almost complete. However, a diminution in COD and TOC removal efficiencies was observed in correspondence to the 4‐aminobenzenesulfonic acid (4‐ABS) accumulation in the bioreactor. Although the oxygen transport rate improved the azo dye mineralization, the results suggest that the removal efficiency of azo dyes was affected by biofilm detachment at relatively high Q_GI and B_V,AZ values. After 225 days of continuous operation of the 2S‐RFBR, eight bacterial strains were isolated from the biofilm attached to the porous support. The identified genera were: Arthrobacter, Variovorax, Agrococcus, Sphingomonas, Sphingopyxis, Methylobacterium, Mesorhizobium, and Microbacterium.     

Proteomic analysis of astrocytic secretion in the mouse. Comparison with the cerebrospinal fluid proteome

Astrocytes, the most abundant cell type in the central nervous system, are intimately associated with synapses. They play a pivotal role in neuronal survival and the brain inflammatory response. Some astrocytic functions are mediated by the secretion of polypeptides. Using a proteomic approach, we have identified more than 30 proteins released by cultured astrocytes. These include proteases and protease inhibitors, carrier proteins, and antioxidant proteins. Exposing astrocytes to brefeldin A, which selectively blocks secretory vesicle assembly, suppressed the release of some of these proteins. This indicates that astrocytes secrete these proteins by a classic vesicular mechanism and others by an alternative pathway. Astrocytes isolated from different brain regions secreted a similar pattern of proteins. However, the secretion of some of them, including metalloproteinase inhibitors and apolipoprotein E, was region-specific. In addition, pro-inflammatory treatments modified the profile of astrocytic protein secretion. Finally, more than two thirds of the proteins identified in the astrocyte-conditioned medium were detectable in the mouse cerebrospinal fluid, suggesting that astrocytes contribute to the cerebrospinal fluid protein content. In conclusion, this study provides the first unbiased characterization of the major proteins released by astrocytes, which may play a crucial role in the modulation of neuronal survival and function.     

The dynamics of three shrub species in a fire-prone temperate savanna: the interplay between the seed bank, seed rain and fire regime

A model was developed to assess how the seed rain and fire regime affect seed bank dynamics and seedling establishment of three native shrub species (Acanthostyles buniifolius, Baccharis pingraea and Baccharis dracunculifolia) with different regeneration strategies, in temperate South American savanna. Seed bank and seed rain were quantified for each species under different fire regimes, and their relative roles in regeneration were evaluated. All species had short-term persistent seed banks and high annual variability in seed production. A high proportion of seeds deposited in the seed rain produced seedlings after fire; few entered the soil seed bank. Fire killed a high proportion of the seeds in the soil seed bank. Seedlings derived from the seed rain had a higher probability of surviving for 2 years than seedlings emerging from the soil seed bank. In the absence of fire, establishment depended on germination both from the seed rain and the soil seed bank, whereas with annual fire, establishment was primarily dependent on germination of seeds arriving in the annual seed rain, regardless of species’ regeneration strategies. These results help to explain changes in the vegetation of South American temperate savannas as a result of changes in fire regime and grazing management during the last 50 years. By revealing the crucial roles of the soil seed bank and seed rain in regeneration, this study provides vital information for the development of appropriate management practices to control populations of shrub species with different regeneration strategies in South American temperate savannas.