Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging

Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii^−/−) mice. The effects of arg-ii^−/− on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from arg-ii^−/− cells, activates fibroblasts to produce various cytokines including TGF-β1 and collagen, which is abolished by IL-1β receptor antagonist or TGF-β type I receptor blocker. Conversely, TGF-β1 or IL-1β also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1β and TGF-β1 in epithelial cells and activation of fibroblasts, which is inhibited in arg-ii^−/− mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1β and TGF-β1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging.     

Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse

Mammalian Genome - Several lines of evidence suggest that the presence of the Y chromosome influences DNA methylation of autosomal loci. To better understand the impact of the Y chromosome on...     

The Ontogeny of Vocal Sequences: Insights from a Newborn Wild Chimpanzee (Pan troglodytes schweinfurthii)

International Journal of Primatology - Observations of early vocal behaviours in non-human primates (hereafter primates) are important for direct comparisons between human and primate vocal...     

Antibiofilm Activity of Invasive Plants against Candida albicans: Focus on Baccharis halimifolia Essential Oil and Its Compounds

The extracts of five invasive plants were investigated for antifungal and antibiofilm activities against Candida albicans, C. glabrata, C. krusei, and C. parapsilosis. The antifungal activity was evaluated using the microdilution assay and the antibiofilm effect by measurement of the metabolic activity. Ethanol and ethanol-water extracts of Reynoutria japonica leaves inhibited 50 % of planktonic cells at 250 μg mL⁻¹ and 15.6 μg mL⁻¹, respectively. Ethanol and ethanol-water extracts of Baccharis halimifolia inhibited >75 % of the mature biofilm of C. albicans at 500 μg mL⁻¹. The essential oil (EO) of B. halimifolia leaves was the most active (50 % inhibition (IC₅₀) at 4 and 74 μg mL⁻¹against the maturation phase and 24 h old-biofilms of C. albicans, respectively). Oxygenated sesquiterpenes were the primary contents in this EO (62.02 %), with β-caryophyllene oxide as the major component (37 %). Aromadendrene oxide-(2), β-caryophyllene oxide, and (±)-β-pinene displayed significant activities against the maturation phase (IC₅₀=9–310 μ mol l⁻¹) and preformed 24 h-biofilm (IC₅₀=38–630 μ mol l⁻¹) of C. albicans with very low cytotoxicity for the first two compounds. C. albicans remained the most susceptible species to this EO and its components. This study highlighted for the first time the antibiofilm potential of B. halimifolia, its EO and some of its components.     

Experimental model for studying the mechanical effects of +Gz accelerations on the brain

Bovine brains were excised and placed into a transparent mold equipped with a pump and perfusion system. This unit was then centrifuged and changes in brain contour were video recorded. Analysis of the resulting images showed that changes occurred in brain structures as a result of crushing. The effects of perfusion on the amount of deformation and other results are discussed.     

Methodology in the study of seabass (Lates calcarifer Bloch): nutritional requirements in Singapore

This paper describes the effort of the Marine Aquaculture Section of the Primary Production Department in Singapore and the Institut Francais de Recherche pour l'Exploitation de la Mer in developing adequate facilities for fish nutritional requirement studies in Singapore, and in introducing appropriate nutritional methodology so that results are reliable and accurate. One of the first achievements was the demonstration of homogeneous fish (tropical seabass, Lates calcarifer Bloch) growth response in a newly established tank system before any nutritional experiments were initiated. The application of statistical procedures that take into consideration the power of a test and number of replications required has allowed for more accurate interpretation of results. This can be seen in the results of the first nutritional requirement experiment on the optimal dietary protein level of the seabass at constant energy.     

Structural modifications of oxidized insulin B-chain induced by glycerol addition

H-NMR studies of the bovine insulin S-sulfonatedB-chain are reported in H₂O/D₂O (9/1) and inglycerol-d₅ (5 M) using two-dimensional NMRspectroscopy. The first results show that the oxidizedinsulin B-chain secondary structure differs from thatof native insulin by a loss of the -helixbetween the two disulfide bridges and that theglycerol favours the structuring of the peptide.     

Long-term gene delivery into the livers of immunocompetent mice with E1/E4-defective adenoviruses.

We have compared the in vitro and in vivo behaviors of a set of isogenic E1- and E1/E4-defective adenoviruses expressing the lacZ gene of Escherichia coli from the Rous sarcoma virus long terminal repeat. Infection of tumor-derived established cell lines of human origin with the doubly defective adenoviruses resulted in (i) a lower replication of the viral backbone that correlated with reduced levels of E2A-specific RNA and protein, (ii) a significant shutoff of late gene and protein expression, and (iii) no apparent virus-induced cytotoxicity. Independently of the extent of the deletion, the additional inactivation of E4 from the viral backbone therefore drastically disabled the virus in vitro, with no apparent effect on transgene expression. A lacZ-transgenic model was used to compare the different recombinant adenoviruses in the livers of C57BL/6 mice. The immune response to the virally encoded beta-galactosidase was minimal in this model, as infusion of the E1-defective adenovirus resulted in a time course of transgene expression that mimicked that in immunodeficient (nu/nu) mice, with very little inflammation and necrosis in the liver. Administration of a doubly defective adenovirus to the transgenic animals led to long-term extrachromosomal persistence of viral DNA in the liver, with no detectable methylation of CpG dinucleotides. However, transient transgene expression was observed independently of the extent of the E4 deletion, suggesting that the choice of the promoter may be critical to maintain transgene expression from these attenuated adenovirus vectors.     

Physical Activity,Obesity, and Cardiovascular Risk Factors in Children. The Belgian Luxembourg Child Study II

GUILLAUME, MICHÈLE, LEIF LAPIDUS, PER BJÖRNTORP, ANDRE LAMBERT. Physical activity, obesity, and cardiovascular risk factors in children. The Belgian Luxembourg Child Study II. Physical activity was measured in relation to cardiovascular (CV) risk factors in a randomly selected population of 1028 children from Province de Luxembourg in Belgium, a mainly rural area with a high prevalence of such risk factors among adults and children. Physical activity was estimated as participation in sport activities, a major indicator of leisure-time physical activity in schoolchildren, and physical inactivity was estimated as frequency and duration of television (TV) watching. Boys participated more frequently in sport activities than girls did (p=0. 001). A majority of the children watched TV daily. After age adjustment, bodyweight (girls, p<0. 012; boys, p<0. 027) and, in boys, body mass index (BMI) (p<0. 039) were related to days per week of TV watching. No significant relationships with other CV risk factors remained after adjustments for BMI. In analyses of independent contributions of age, TV watching, and sports activity on CV risk factors, age showed highly significant relationships. In boys, TV showed relationships with BMI (P<0. 04) and (borderline) with systolic blood pressure, independent of age and sports activity, whereas the latter was significantly related to subscapular skinfold (p<0. 04) and (borderline) with triceps skinfold and cholesterol. In girls, no significant independent contributions to risk factor associations were found. The father's education was directly associated with sports activities, whereas the mother being a housewife showed negative relationships to physical activity and positive to TV watching in their children, suggesting socioeconomic influence on the activity patterns of children. Furthermore, registrations suggested less physical activity in the most rural part of the area. It is concluded that children in this mainly rural area watch TV frequently. In boys, physical inactivity, measured both as TV watching and as registrations of sports activities, contributes independently to body fat mass. In girls, no contribution or weaker contributions of physical inactivity were found. This suggests that contributory factors leading to obesity might be different in girls and boys.     

Insights on the amino acid side-chain interactions of a synthetic T-cell determinant.

The effect of single amino acid substitutions at positions 18 and 20 on the T-cell determinant (TD) character of peptide p12-26 from lambda repressor protein and on its recognition by a monoclonal antibody was studied by means of 40 synthetic peptides of a length of 15 amino acids. ELISA competition experiments showed that the identity of amino acid at position 20 is very important for antibody recognition, whereas that of amino acid at position 18 is much less important. In contrast, both Leu 18 and Ala 20 are important residues in defining the TD character of peptide p12-26. The most tolerated replacements, ordered in increasing disrupting power are: Ala 20 by Cys, Ser or Gly and Leu 18 by Ile or Val. Any other amino acid replacement completely abolishes the TD capacity of peptide p12-26. The peptides used in this study were synthesized using a multiple solid-phase peptide synthesizer newly designed. Their purity was very high as shown by amino acid sequence experiments.