Short-term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. Air Pollution and Health: a European Approach.

OBJECTIVES: To carry out a prospective combined quantitative analysis of the associations between all cause mortality and ambient particulate matter and sulphur dioxide. DESIGN: Analysis of time series data on daily number of deaths from all causes and concentrations of sulphur dioxide and particulate matter (measured as black smoke or particles smaller than 10 microns in diameter (PM10)) and potential confounders. SETTING: 12 European cities in the APHEA project (Air Pollution and Health: a European Approach). MAIN OUTCOME MEASURE: Relative risk of death. RESULTS: In western European cities it was found that an increase of 50 micrograms/m3 in sulphur dioxide or black smoke was associated with a 3% (95% confidence interval 2% to 4%) increase in daily mortality and the corresponding figure for PM10 was 2% (1% to 3%). In central eastern European cities the increase in mortality associated with a 50 micrograms/m3 change in sulphur dioxide was 0.8% (-0.1% to 2.4%) and in black smoke 0.6% (0.1% to 1.1%). Cumulative effects of prolonged (two to four days) exposure to air pollutants resulted in estimates comparable with the one day effects. The effects of both pollutants were stronger during the summer and were mutually independent. CONCLUSIONS: The internal consistency of the results in western European cities with wide differences in climate and environmental conditions suggest that these associations may be causal. The long term health impact of these effects is uncertain, but today''s relatively low levels of sulphur dioxide and particles still have detectable short term effects on health and further reductions in air pollution are advisable.     

Deoxyribose degradation catalyzed by Fe(III)-EDTA: kinetic aspects and potential usefulness for submicromolar iron measurements

Iron ions play a central role in ·OH radicals formation and induction of oxidative stress in living organisms. Ironcatalyzed ·OH radical formation degrades deoxyribose to thiobarbituric acid reactive substances (TBA-RS). This paper analyzes kinetic properties of the Fe(III)-EDTA-catalyzed deoxyribose degradation in the presence of ascorbate. The yield of TBA-RS formation in the presence of EDTA was 4-fold higher than in its absence, contrasting with results reported elsewhere, Cu(II)-EDTA and Fe(III)-citrate were unable to catalyze deoxyribose degradation. The dependence on deoxyribose concentration was fitted to a Lineweaver Burk-like plot and it was calculated that approximately 4.5 mM deoxyribose scavenged half of the ·OH radicals formed. The data for Fe(III)-EDTA concentration dependence could also be fitted to a rectangular hyperbolic function. This function was linear up to 1 M added FeCl₃ and this property could be utilized as an assay for the estimation of submicromolar iron concentrations. Submicromolar concentrations of iron could induce measurable yields of TBA-RS. Differences of as little as 0.1 M Fe(III)-EDTA could be reproducibly detected under optimum experimental conditions, above a consistent background absorbance that was equivalent to 0.35±0.05 M Fe(III)-EDTA and represented contaminating iron in the reactants that could not be removed with Chelex-100. The low method determination limit makes the deoxyribose degradation reaction potentially useful as a new, highly sensitive and cost effective assay for iron quantification.     

SHP‐2 Phosphatase Prevents Colonic Inflammation by Controlling Secretory Cell Differentiation and Maintaining Host‐Microbiota Homeostasis

Polymorphisms in the PTPN11 gene encoding for the tyrosine phosphatase SHP‐2 were described in patients with ulcerative colitis. We have recently demonstrated that mice with an intestinal epithelial cell‐specific deletion of SHP‐2 (SHP‐2^IEC‐KO) develop severe colitis 1 month after birth. However, the mechanisms by which SHP‐2 deletion induces colonic inflammation remain to be elucidated. We generated SHP‐2^IEC‐KO mice lacking Myd88 exclusively in the intestinal epithelium. The colonic phenotype was histologically analyzed and cell differentiation was determined by electron microscopy and lysozyme or Alcian blue staining. Microbiota composition was analyzed by 16S sequencing. Results show that innate defense genes including those specific to Paneth cells were strongly up‐regulated in SHP‐2‐deficient colons. Expansion of intermediate cells (common progenitors of the Goblet and Paneth cell lineages) was found in the colon of SHP‐2^IEC‐KO mice whereas Goblet cell number was clearly diminished. These alterations in Goblet/intermediate cell ratio were noticed 2 weeks after birth, before the onset of inflammation and were associated with significant alterations in microbiota composition. Indeed, an increase in Enterobacteriaceae and a decrease in Firmicutes were observed in the colon of these mice, indicating that dysbiosis also occurred prior to inflammation. Importantly, loss of epithelial Myd88 expression inhibited colitis development in SHP‐2^IEC‐KO mice, rescued Goblet/intermediate cell ratio, and prevented NFκB hyperactivation and inflammation. These data indicate that SHP‐2 is functionally important for the maintenance of appropriate barrier function and host‐microbiota homeostasis in the large intestine. J. Cell. Physiol. 231: 2529–2540, 2016. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.     

Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, we took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which we developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, we observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [3H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin in supporting cell proliferation is to supply cells with iron.     

In vitro anti-microbial activity of extracts from the callus cultures of some Nigella species

Crude methanol extracts from callus cultures of Nigella arvensis, N. damascena, N. hispanica, N. integrifolia, and N. sativa were investigated for their anti-microbial activity. Growth inhibition was determined in Gram-positive and Gram-negative bacterial strains as well as in yeast by using a broth-microdilution method. The results showed that the extracts of all calli tested exhibited significant anti-microbial activity, especially against Bacillus cereus, Staphylococcus aureus and Staphylococcus epidermidis. Compared with other Nigella species, a callus culture of N. hispanica was the most effective against the microorganisms used in this study.     

Population biology of two rare fern species: long life and long-lasting stability

? Premise of the study: This study describes the population dynamics of two rare fern species and evaluates the prospects of their survival. This is the first detailed demography study of ferns using transition matrix models. The study species, Asplenium adulterinum and A. cuneifolium, are restricted to serpentine rocks and differ in ploidy level and partly in habitat requirements. Both species are of interest in nature conservation. ? Methods: Single life-history traits were evaluated and transition matrix models were used to describe the dynamics of the populations. Population growth rates, elasticity values, and life-table response experiments were used to compare the dynamics between species, years, and different habitat types. Predicted population performance based on models was compared with real data on population growth. ? Key Results: All populations of both species are growing. Stable stage distribution based on stochastic simulation corresponds to current stage distribution. The most critical phase of the life cycle is stasis of large adult plants. Reproduction is of low importance. Extinction probability of small populations is low. Mean life span of individuals of both species is 30-50 yr. When compared with real data, the model successfully predicted population performance over 10 yr. ? Conclusion: Populations in the study region are not endangered, and current population dynamics are stable. Differences in life-history traits between species, probability of extinction between species and habitat, and different ploidy-and, thus, probably different dispersal ability-suggest the existence of metapopulation dynamics.     

Differential Induction of Antimicrobial REGIII by the Intestinal Microbiota and Bifidobacterium breve NCC2950

The intestinal microbiota is a key determinant of gut homeostasis, which is achieved, in part, through regulation of antimicrobial peptide secretion. The aim of this study was to determine the efficiency by which members of the intestinal microbiota induce the antimicrobial peptide REGIII and to elucidate the underlying pathways. We showed that germfree mice have low levels of REGIII-γ in their ileum and colon compared to mice with different intestinal microbiota backgrounds. Colonization with a microbiota of low diversity (altered Schaedler flora) did not induce the expression of REGIII-γ as effectively as a complex community (specific pathogen free). Monocolonization with the probiotic Bifidobacterium breve, but not with the nonprobiotic commensal Escherichia coli JM83, upregulated REGIII-γ expression. Induction of REGIII-γ by B. breve was abrogated in mice lacking MyD88 and Ticam1 signaling. Both live and heat-inactivated B. breve but not spent culture medium from B. breve induced the expression of REGIII-α, the human ortholog and homolog of REGIII-γ, in human colonic epithelial cells (Caco-2). Taken together, the results suggest that REGIII-γ expression in the intestine correlates with the richness of microbiota composition. Also, specific bacteria such as Bifidobacterium breve NCC2950 effectively induce REGIII production in the intestine via the MyD88-Ticam1 pathway. Treatment with this probiotic may enhance the mucosal barrier and protect the host from infection and inflammation.