The role of PGR5 in the redox poising of photosynthetic electron transport

The pgr5 mutant of Arabidopsis thaliana has been described as being deficient in cyclic electron flow around photosystem I, however, the precise role of the PGR5 protein remains unknown. To address this issue, photosynthetic electron transport was examined in intact leaves of pgr5 and wild type A. thaliana. Based on measurements of the kinetics of P700 oxidation in far red light and re-reduction following oxidation in the presence of DCMU, we conclude that this mutant is able to perform cyclic electron flow at a rate similar to the wild type. The PGR5 protein is therefore not essential for cyclic flow. However, cyclic flow is affected by the pgr5 mutation under conditions where this process is normally enhanced in wild type leaves, i.e. high light or low CO₂ concentrations resulted in enhancement of cyclic electron flow. This suggests a different capacity to regulate cyclic flow in response to environmental stimuli in the mutant. We also show that the pgr5 mutant is affected in the redox poising of the chloroplast, with the electron transport chain being substantially reduced under most conditions. This may result in defective feedback regulation of photosynthetic electron transport under some conditions, thus providing a rationale for the reduced efficiency of cyclic electron flow.     

Identification of a good c-myc antisense oligodeoxynucleotide target site and the inactivity at this site of novel NCH triplet--targeting ribozymes.

A region of c-myc mRNA was identified which permitted very efficient antisense effects to be achieved in living cells using chimeric methylphosphonate--phosphodiester antisense effectors. Novel inosine--containing ribozymes (which cleave after NCH triplets) were directed to an ACA triplet within this region and delivered into living cells. No ribozyme intracellular activity could be identified. Very low ribozyme function was also observed in in vitro assays using a 1700nt substrate RNA.     

Macrophage polarization state affects lipid composition and the channeling of exogenous fatty acids into endogenous lipid pools

Adipose-tissue-resident macrophages (ATMs) maintain metabolic homeostasis but also contribute to obesity-induced adipose tissue inflammation and metabolic dysfunction. Central to these contrasting effects of ATMs on metabolic homeostasis is the interaction of macrophages with fatty acids. Fatty acid levels are increased within adipose tissue in various pathological and physiological conditions, but appear to initiate inflammatory responses only upon interaction with particular macrophage subsets within obese adipose tissue. The molecular basis underlying these divergent outcomes is likely due to phenotypic differences between ATM subsets, although how macrophage polarization state influences the metabolism of exogenous fatty acids is relatively unknown. Herein, using stable isotope-labeled and nonlabeled fatty acids in combination with mass spectrometry lipidomics, we show marked differences in the utilization of exogenous fatty acids within inflammatory macrophages (M1 macrophages) and macrophages involved in tissue homeostasis (M2 macrophages). Specifically, the accumulation of exogenous fatty acids within triacylglycerols and cholesterol esters is significantly higher in M1 macrophages, while there is an increased enrichment of exogenous fatty acids within glycerophospholipids, ether lipids, and sphingolipids in M2 macrophages. Finally, we show that functionally distinct ATM populations in vivo have distinct lipid compositions. Collectively, this study identifies new aspects of the metabolic reprogramming that occur in distinct macrophage polarization states. The channeling of exogenous fatty acids into particular lipid synthetic pathways may contribute to the sensitivity/resistance of macrophage subsets to the inflammatory effects of increased environmental fatty acid levels.     

Geographic Variation in the Prevalence of Obesity,Diabetes, and Obesity‐Related Behaviors**

Objective: To examine the variation in the prevalences of obesity and type 2 diabetes in weight loss counseling by health providers and in other potential obesity‐related determinants in 100 metropolitan statistical areas in the United States. Research Methods and Procedures: We performed a cross‐sectional study using data from the 2000 Behavioral Risk Factor Surveillance System, the largest telephone survey of health behaviors in the United States, of age‐adjusted prevalence of obesity, type 2 diabetes, intake of ≥five servings of fruits and vegetables per day, participation in 150 minutes of leisure‐time physical activity per week, receipt of weight management advice, and reports of trying to lose or maintain weight among men and women more than 18 years old. Results: The age‐adjusted prevalence of obesity ranged from 13.1% to 30.0% and that of type 2 diabetes from 3.3% to 9.2%. Among participants who had visited a physician for a routine checkup in the previous 12 months, 13.1% to 27.1% of all participants recalled receiving advice from a health professional about their weight, and 11.7% to 34.6% of overweight or obese participants recalled receiving advice to maintain or lose weight. Discussion: Significant differences in the prevalence of obesity and self‐reported type 2 diabetes and in medical practice patterns regarding weight management advice exist among metropolitan statistical areas. These results suggest important opportunities to investigate reasons for these variations that could potentially be used to mitigate the current epidemic of obesity and to identify areas where obesity and diabetes prevention efforts may need to be targeted.