Journal of Environmental Economics and Management 45 (2003) 294-318. doi:10.1016/S0095-0696(02)00054-22016-03-04T18:46:49

No abstract

The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing.

No abstract

Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays.Salmonella enterica serotype Typhi is a human-restricted pathogen that is the primary cause of enteric fever. It is estimated that S. Typhi infects over 20 million individuals and kills approximately 200,000 people globally each year (4). Currently, commercially available typhoid vaccines provide approximately 50 to 75% protection for 2 to 5 years (21), although an anti-typhoid Vi conjugate vaccine demonstrated 90% protection in 2-to 5-year-old children in a large field trial (23). Available and practical diagnostic tests for typhoid fever lack sensitivity and/or specificity (28). Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines.Infection with S. Typhi begins with the ingestion of contaminated water or food. The bacteria invade the gastrointestinal mucosa, translocate to the lymphoid follicles, where they survive and replicate within macrophages, and then disseminate via the bloodstream to the liver, spleen, and intestinal lymph nodes (14). The incubation period is typically 8 to 14 days (22), and symptoms include fever, abdominal pain, anorexia, weakness, potential complications of intestinal perforation, encephalopathy, and gastrointestinal bleeding (14,34). Clinical studies demonstrate that S. Typhi infection stimulates both an intestinal mucosa...