Both the Notch and TCR signaling pathways play an important role in T cell development, but the links between these signaling pathways are largely unexplored. The adapter protein Numb is a well-characterized inhibitor of Notch and also contains a phosphotyrosine binding domain, suggesting that Numb could provide a link between these pathways. We explored this possibility by investigating the physical interactions among Notch, Numb, and the TCR signaling apparatus and by examining the consequences of a Numb mutation on T cell development. We found that Notch and Numb cocluster with the TCR at the APC contact during Ag-driven T cell-APC interactions in both immature and mature T cells. Furthermore, Numb coimmunoprecipitates with components of the TCR signaling apparatus. Despite this association, T cell development and T cell activation occur normally in the absence of Numb, perhaps due to the expression of the related protein, Numblike. Together our data suggest that Notch and TCR signals may be integrated at the cell membrane, and that Numb may be an important adapter in this process.

No abstract

Mycobacterium sp strain CH-2 was isolated from a manufactured gas plant contaminated with polycyclic aromatic hydrocarbons (PAHs) and was identified by analysis of 16S rDNA sequences. Strain CH-2 was capable of mineralizing 3- and 4- ring PAHs, including phenanthrene, pyrene, and fluoranthene. In addition, strain CH-2 could utilize phenanthrene, pyrene and a wide range of alkanes as a sole carbon and energy source. Primers based upon the sequences of the polycyclic aromatic hydrocarbon (PAH) dioxygenases nidAB (from Mycobacterium vanbaalenii strain PYR-1) and pdoA2B2 (from Mycobacterium sp. Strain 6PY1) were used as molecular probes to amplify the dioxygenases. Degenerate primers were used to amplify a portion of an alkane monooxygenase gene. Mineralization assays and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that the alkane monooxygenase was constitutively expressed, while nidAB and pdoA2B2 were expressed only in the presence of PAHs. A genomic library of strain CH-2 was created and then screened for the presence of biodegradative operons using the amplified PAH dioxygenases. The pdolocus included a partial pdoF, as well as pdoA2, pdoB2, orf 72, and putative genes for a ferredoxin, an araC-type regulator, and a reductase. The nid locus included a partial nidC, as well as nidB, nidA, and a putative promoter. Primer extension analysis of the nidlocus located the transcriptional start site 68bp upstream of the nidB start codon. The putatively identified promoter region and a promoter fragment lacking the -10 region were amplified, and the products were cloned into pRW50. This plasmid carries the lac operon without a promoter. The plasmid containing the full length promoter expressed the lacZ reporter gene, while expression by the promoter fragment was equivalent to the expression of cells carrying pRW50.

Background: Central Nervous System (CNS) infections caused by bacteria and resulting immune responses could underlie neurodegenerative diseases such as Alzheimer's disease (AD). Neuroinflammation is a well-known component of AD furthering disease pathology and progression. However, the mechanisms by which infectious agents con-