Differences in indoor versus outdoor concentrations of ultrafine particles, PM2.5, PMabsorbance and NO2 in Swiss homes.

Indoor air quality is a growing concern as we spend the majority of time indoors and as new buildings are increasingly airtight for energy saving purposes. For a better understanding of residential indoor air pollution in Switzerland we conducted repeated 1-2-week-long indoor and outdoor measurements of particle number concentrations (PNC), particulate matter (PM), light absorbance of PM2.5 (PMabsorbance) and nitrogen dioxide (NO2). Residents of all homes were enrolled in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Indoor levels were comparable in urban areas and generally low in rural homes. Average indoor levels were 7800 particles/cm(3) (interquartile range=7200); 8.7 µg/m(3) (6.5) PM2.5 and 10.2 µg/m(3) (11.2) NO2. All pollutants showed large variability of indoor/outdoor ratios between sites. We observed similar diurnal patterns for indoor and outdoor PNC. Nevertheless, the correlation of average indoor and outdoor PNC between sites as well as longitudinal indoor/outdoor correlations within sites were low. Our results show that a careful evaluation of home characteristics is needed when estimating indoor exposure to pollutants with outdoor origin.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers.

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, both of which have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hr periods from a total of 50 observation days. We measured their exposure to fine particulate matter (diameter ≤ 2.5 µm; PM2.5), ultrafine particles, and noise, and the cardiopulmonary health end points: blood pressure, proinflammatory and prothrombotic markers in the blood, lung function, and fractional exhaled nitric oxide (FeNO) measured approximately 15 hr after work. Heart rate variability was assessed during a sleep period approximately 10 hr after work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and was negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased high-frequency and low-frequency power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and nonsignificantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.

Th17 cells have been recognized as the central effectors in organ-related autoimmune diseases. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3(+) Treg differentiation by inhibition of TGF-beta induced Foxp3 and induction of RORgammat, a Th17 lineage-specific transcription factor. Recently IL-21 has been suggested to induce RORgammat and Th17 development in the absence of IL-6. However, the relevance of IL-21 for Th17-dependent inflammatory responses in vivo remains unclear. In this study, we demonstrate that differentiation of IL-17-producing CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R(-/-) and il21(-/-) mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and autoimmune myocarditis. IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R.

A calcium-gated lid and a large beta-roll sandwich are revealed by the crystal structure of extracellular lipase from Serratia marcescens.

Lipase LipA from Serratia marcescens is a 613-amino acid enzyme belonging to family I.3 of lipolytic enzymes that has an important biotechnological application in the production of a chiral precursor for the coronary vasodilator diltiazem. Like other family I.3 lipases, LipA is secreted by Gram-negative bacteria via a type I secretion system and possesses 13 copies of a calcium binding tandem repeat motif, GGXGXDXUX (U, hydrophobic amino acids), in the C-terminal part of the polypeptide chain. The 1.8-A crystal structure of LipA reveals a close relation to eukaryotic lipases, whereas family I.1 and I.2 enzymes appear to be more distantly related. Interestingly, the structure shows for the N-terminal lipase domain a variation on the canonical alpha/beta hydrolase fold in an open conformation, where the putative lid helix is anchored by a Ca(2+) ion essential for activity. Another novel feature observed in this lipase structure is the presence of a helical hairpin additional to the putative lid helix that exposes a hydrophobic surface to the aqueous medium and might function as an additional lid. The tandem repeats form two separated parallel beta-roll domains that pack tightly against each other. Variations of the consensus sequence of the tandem repeats within the second beta-roll result in an asymmetric Ca(2+) binding on only one side of the roll. The analysis of the properties of the beta-roll domains suggests an intramolecular chaperone function.

The molecular architecture of the metalloprotease FtsH.

The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.