Contamination of the environment with mercury has been an important concern throughout the world for decades. Exposure to high Hg levels can be harmful to the brain, heart, kidneys, lungs, and immune system of humans of all ages. Driven by the need to detect trace amounts of mercury in environmental samples, here we present a miniaturized, inexpensive, and battery-operated ultrasensitive gold nanoparticle-based nanomaterial surface energy transfer probe for screening mercury levels in contaminated soil, water, and fish which has excellent sensitivity (2 ppt) and selectivity for Hg(II) over competing analytes, with the largest fluorescence enhancement to date for sensing Hg(II) in environmental samples (1100-fold). The sensitivity of our probe to detect mercury level in soil, water, and fish is about 2-3 orders of magnitude higher than the EPA standard limit. We demonstrate that our probe is suitable to screen the amount of mercury in different fish, shellfish, and water samples from various commercial sources.

T-cell costimulation and coinhibition generated by engagement of the B7 family and their receptor CD28 family are of central importance in regulating the T-cell response, making these pathways very attractive therapeutic targets. Here we describe HERV-H LTRassociating protein 2 (HHLA2) as a member of the B7 family that shares 10-18% amino acid identity and 23-33% similarity to other human B7 proteins and phylogenetically forms a subfamily with B7x and B7-H3 within the family. HHLA2 is expressed in humans but not in mice, which is unique within the B7 and CD28 families. HHLA2 protein is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation with LPS and IFN-γ. HHLA2 does not interact with other known members of the CD28 family or the B7 family, but does bind a putative receptor that is constitutively expressed not only on resting and activated CD4 and CD8 T cells but also on antigen-presenting cells. HHLA2 inhibits proliferation of both CD4 and CD8 T cells in the presence of T-cell receptor signaling. In addition, HHLA2 significantly reduces cytokine production by T cells including IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17A, and IL-22. Thus, we have identified a unique B7 pathway that is able to inhibit human CD4 and CD8 T-cell proliferation and cytokine production. This unique human T-cell coinhibitory pathway may afford unique strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may help to design better vaccines. Interactions between members of the B7 ligand and CD28 receptor families generate positive costimulation and negative coinhibition, which are of central importance in regulating T-cell responses (1-3). B7-1/B7-2/CD28/CTLA-4 is the most extensively characterized of these pathways. Ligands B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs) bind to CD28 on naïve T cells and provide a major costimulatory signal to activate naïve T cells. After the initial activation, coinhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4, CD152) is induced on T cells and engages the same B7-1 and B7-2 ligands to restrain T-cell function. In contrast to the costimulatory activity of CD28, the interaction of B7-1 or B7-2 with CTLA-4 is essential for limiting the proliferative response of recently activated T cells to antigen and CD28-mediated costimulation.During the past decade, several new pathways in the B7 and CD28 families have been identified, including B7h/ICOS, PD-L1/PD-L2/PD-1, B7-H3/receptor, and B7x/receptor. B7h (4) (also called ICOS-L, B7RP-1 (5), GL50 (6), B7H2 (7), LCOS (8), and CD275) binds to the inducible costimulator (ICOS, CD278) on activated T cells (9), which induces strong phosphatidylinositol 3-kinase activity (10, 11) and leads to the expression of transcription factors involved in follicular helper CD4 T (Tfh) differentiation (12). Therefore, the B7h/ICOS pathway provides critical T-cell help to B cells. Deficiencies in this pathway result in substantially reduced numbers of mem...

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The nanoscience revolution that sprouted throughout the 1990s is having great impact in current and future DNA detection technology around the world. In this review, we report our recent progress on gold nanoparticle based fluorescence resonance energy transfer assay to monitor DNA hybridization as well as the cleavage of DNA by nucleases. We tried to discuss a reasonable account of the science and the important fundamental work carried out in this area. We also report the development of a compact, highly specific, inexpensive and user-friendly optical fiber laser-induced fluorescence sensor based on fluorescence quenching by nanoparticles to detect singlestrand DNA hybridization at femtomolar level.

Background-Pseudomonas aeruginosa may undergo a phenotypic change from the wild (prototrophic) type to an auxotrophic phenotype in the course of respiratory infection in patients with cystic fibrosis. The clinical significance of this is unclear. A study was undertaken to investigate whether the presence of auxotrophs of P aeruginosa in the sputum of patients with cystic fibrosis correlated with severity of respiratory disease, and whether increased sputum concentrations of amino acids were associated with the emergence of these forms. Methods-Sixty adult patients with cystic fibrosis, colonised by P aeruginosa, were recruited and baseline clinical data including lung function were recorded. Serial sputum samples were obtained before, during, and after infective exacerbations where possible. These samples were used for routine microbiological culture, assessment of auxotrophy of P aeruginosa, measurement of amino acid content, and neutrophil elastase assay. Conclusions-P aeruginosa frequently exhibits auxotrophy in patients with cystic fibrosis, particularly in those with severe underlying pulmonary disease. The sputum amino acid content of patients with cystic fibrosis is high during infective exacerbations and correlates with pulmonary disease severity. (Thorax 2000;55:795-797) Results-Auxotrophy