Mycobacterium tuberculosis parasitizes resting macrophages yet is killed by activated macrophages through both oxidative and nonoxidative mechanisms. Nonoxidative mechanisms are linked to the maturation of the bacteria-containing phagosome into an acidified, hydrolytically active compartment. We describe here a mechanism for killing Mycobacteria in the lysosomal compartment through the activity of peptides generated by the hydrolysis of ubiquitin. The induction of autophagy in infected macrophages enhanced the delivery of ubiquitin conjugates to the lysosome and increased the bactericidal capacity of the lysosomal soluble fraction. The accumulation of ubiquitinated proteins in the autophagolysosome provides one possible mechanism behind the antimicrobial activities observed for a range of pathogens in autophagous host cells.macrophage ͉ phagosome ͉ tuberculosis ͉ lysosome

Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12-IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast,

Detection of Cu(2+) ions and study of their subcellular distribution in physiological processes are of considerable significance because of their potential environmental and biological applications. Some fluorescence based sensors have been developed for selective detection of Cu(2+) ions, based on organic fluorescent probes that specifically bind to Cu(2+) ions. However, these sensors are not suitable for detection in biological samples due to the short penetration depth of UV/visible light used to excite the fluorescent probes. The use of near-infrared (NIR) light can afford penetration depths of an order of magnitude greater than that of visible light, however, a material that can convert NIR light to visible light is required. A facile method has been developed for in-depth detection of Cu(2+) ions based on fluorescence upconversion. A mesoporous silica shell is coated on upconversion nanoparticles (UCNPs) and a Cu(2+) ion sensitive fluorescent probe, rhodamine B hydrazide, is incorporated into the mesoporous silica. Upon excitation by a NIR light, the UCNPs emit visible light to excite the Cu(2+)-sensitive fluorescent probe. Because of the unique optical properties of UCNPs and their ability to convert NIR light to visible light, this is a feasible method for sensitive and in-depth detection of Cu(2+) ions in a complex biological or environmental sample due to the low autofluorescence and the high penetration depth of NIR light.

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A renewed interest in non-coding RNA (ncRNA) has led to the discovery of novel RNA species and post-transcriptional ribonucleoside modifications, and an emerging appreciation for the role of ncRNA in RNA epigenetics. Although much can be learned by amplification-based analysis of ncRNA sequence and quantity, there is a significant need for direct analysis of RNA, which has led to numerous methods for purification of specific ncRNA molecules. However, no single method allows purification of the full range of cellular ncRNA species. To this end, we developed a multidimensional chromatographic platform to resolve, isolate and quantify all canonical ncRNAs in a single sample of cells or tissue, as well as novel ncRNA species. The applicability of the platform is demonstrated in analyses of ncRNA from bacteria, human cells and plasmodium-infected reticulocytes, as well as a viral RNA genome. Among the many potential applications of this platform are a system-level analysis of the dozens of modified ribonucleosides in ncRNA, characterization of novel long ncRNA species, enhanced detection of rare transcript variants and analysis of viral genomes.