Organic nitrogen in PM2.5 aerosol at a forest site in the Southeast US

There is growing evidence that organo-nitrogen compounds may constitute a significant fraction of the aerosol nitrogen (N) budget. However, very little is known about the abundance and origin of this aerosol fraction. In this study, the concentration of organic nitrogen (ON) and major inorganic ions in PM2.5 aerosol were measured at the Duke Forest Research Facility near Chapel Hill, NC, during January and June of 2007. A novel on-line instrument was used, which is based on the Steam Jet Aerosol Collector (SJAC) coupled to an on-line total carbon/total nitrogen analyzer and two on-line ion chromatographs. The concentration of ON was determined by tracking the difference in concentrations of total nitrogen and of inorganic nitrogen (determined as the sum of N-ammonium and N-nitrate). The time resolution of the instrument was 30 min with a detection limit for major aerosol components of ∼0.1 mu;gm-3. Nitrogen in organic compounds contributed ∼33% on average to the total nitrogen concentration in PM2.5, illustrating the importance of this aerosol component. Absolute concentrations of ON, however, were relatively low (lt;1.0 mu;gm-3) with an average of 0.16 mu;gm-3. The absolute and relative contribution of ON to the total aerosol nitrogen budget was practically the same in January and June. In January, the concentration of ON tended to be higher during the night and early morning, while in June it tended to be higher during the late afternoon and evening. Back-trajectories and correlation with wind direction indicate that higher concentrations of ON occur in air masses originating over the continental US, while marine air masses are characterized by lower ON concentrations. The data presented in this study suggests that ON has a variety of sources, which are very difficult to quantify without information on chemical composition of this important aerosol fraction.

Redox rhythm reinforces the circadian clock to gate immune response.

Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.