Mycobacterium tuberculosis acg Gene Is Required for Growth and Virulence In Vivo

Mycobacterium tuberculosis dosRS two-component regulatory system controls transcription of approximately 50 genes including hspX, acg and Rv2030c, in response to hypoxia and nitric oxide conditions and within macrophages and mice. The hspX lies between acg and Rv2030c. However, the functions of the dosR regulated genes in vitro and in vivo are largely unknown. Previously, we demonstrated that deletion of hspX gene produced a mutant which grew faster in macrophages and in mice. In this study, we attempted to determine the functions of acg and Rv2030c by gene inactivation. We demonstrate that Rv2030c is dispensable for virulence and growth. However, deletion of acg produced a mutant which is attenuated in both resting and activated macrophages and in acute and persistent murine infection models. Surprisingly, deletion of acg did not compromise the viability of the mutant to nitrosative and oxidative stresses in vitro and in vivo. In addition, when the WT and the acg mutants were treated with antibiotics such as the prodrugs nitrofurantoin and nitrofuran, the acg mutant became more sensitive than the WT strain to these drugs. This suggests that Acg may not function as a nitroreductase. These data indicate that acg encodes an essential virulence factor for M. tuberculosis and enables it to grow and survive in macrophages and in mouse organs

Diagnosis and management of bone fragility in diabetes: an emerging challenge

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk

Birch pollen rupture and the release of aerosols of respirable allergens

Backgound Birch pollen allergens have been implicated as asthma triggers; however, pollen grains are too large to reach the lower airways where asthmatic reactions occur. Respirable-sized particles containing birch pollen allergens have been detected in air filters, especially after rainfall but the source of these particles has remained speculative.Objective To determine the processes by which birch pollen allergens become airborne particles of respirable size with the potential to contribute to airways inflammation.Methods Branches with attached male catkins were harvested and placed in a controlled emission chamber. Filtered dry air was passed through the chamber until the anthers opened, then they were humidified for 5 h and air-dried again. Flowers were disturbed by wind generated from a small electric fan. Released particles were counted, measured and collected for immuno-labelling and high-resolution microscopy.Results Birch pollen remains on the dehisced anther and can rupture in high humidity and moisture. Fresh pollen takes as long as 3 h to rupture in water. Drying winds released an aerosol of particles from catkins. These were fragments of pollen cytoplasm that ranged in size from 30 nm to 4 &mu;m and contained Bet v 1 allergens.Conclusion When highly allergenic birch trees are flowering and exposed to moisture followed by drying winds they can produce particulate aerosols containing pollen allergens. These particles are small enough to deposit in the peripheral airways and have the potential to induce an inflammatory response.<br /