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Fatty acid amides constitute a large and diverse class of lipid transmitters that includes the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. The magnitude and duration of fatty acid amide signaling are controlled by enzymatic hydrolysis in vivo. Fatty acid amide hydrolase (FAAH) activity in mammals has been primarily attributed to a single integral membrane enzyme of the amidase signature (AS) family. Here, we report the functional proteomic discovery of a second membrane-associated AS enzyme in humans that displays FAAH activity. The gene that encodes this second FAAH enzyme was found in multiple primate genomes, marsupials, and more distantly related vertebrates, but, remarkably, not in a number of lower placental mammals, including mouse and rat. The two human FAAH enzymes, which share 20% sequence identity and are referred to hereafter as FAAH-1 and FAAH-2, hydrolyzed primary fatty acid amide substrates (e.g. oleamide) at equivalent rates, whereas FAAH-1 exhibited much greater activity with N-acyl ethanolamines (e.g. anandamide) and N-acyl taurines. Both enzymes were sensitive to the principal classes of FAAH inhibitors synthesized to date, including O-aryl carbamates and ␣-keto heterocycles. These data coupled with the overlapping, but distinct tissue distributions of FAAH-1 and FAAH-2 suggest that these proteins may collaborate to control fatty acid amide catabolism in primates. The apparent loss of the FAAH-2 gene in some lower mammals should be taken into consideration when extrapolating genetic or pharmacological findings on the fatty acid amide signaling system across species.The fatty acid amide family of bioactive lipids can be divided into at least three chemical classes: N-acylethanolamines (1) and modulates several neurobehavioral processes, including pain (4), feeding (5), and memory (6). Oleamide is a sleep-inducing lipid that accumulates in the cerebrospinal fluid of sleep-deprived animals (2, 7). Oleamide has been shown to affect several protein receptors, including serotonin (8), GABA (9, 10) and cannabinoid (11) receptors, as well as gap junctions (12), and at least a subset of these proteins appears to be critical for mediating the hypnotic effects of oleamide (13,14). NATs are representative members of a large family of N-acyl amino acids that vary in both acyl chain and amino acid content (3, 15-17). These lipids have been shown to modulate pain sensation (17) and activate TRP channels (16).The signaling function of fatty acid amides is terminated by enzymatic hydrolysis in vivo. A principal enzyme involved in this process is fatty acid amide hydrolase (FAAH) (18 -20). Mice with a targeted disruption in the FAAH gene (FAAH(Ϫ/Ϫ) mice) (21) or those treated with FAAH inhibitors (22, 23) are severely impaired in their ability to degrade fatty acid amides and show hypersensitivity to the pharmacological effects of these lipids. Blockade of FAAH activity also leads to highly elevated endogenous levels of fatty acid amides in the nervous system (21-23) and periph...

Nanoscale structures need to be arranged into well-defined configurations in order to build integrated systems. Here we use a chemical-vapour deposition method with gas-phase catalyst delivery to direct the assembly of carbon nanotubes in a variety of predetermined orientations onto silicon/silica substrates, building them into one-, two- and three-dimensional arrangements. The preference of nanotubes to grow selectively on and normal to silica surfaces forces them to inherit the lithographically machined template topography of their substrates, allowing the sites of nucleation and the direction of growth to be controlled.

Achieving information content of satisfactory breadth and depth remains a formidable challenge for proteomics. This problem is particularly relevant to the study of primary human specimens, such as tumor biopsies, which are heterogeneous and of finite quantity. Here we present a functional proteomics strategy that unites the activity-based protein profiling and multidimensional protein identification technologies (ABPP-MudPIT) for the streamlined analysis of human samples. This convergent platform involves a rapid initial phase, in which enzyme activity signatures are generated for functional classification of samples, followed by in-depth analysis of representative members from each class. Using this two-tiered approach, we identified more than 50 enzyme activities in human breast tumors, nearly a third of which represent previously uncharacterized proteins. Comparison with cDNA microarrays revealed enzymes whose activity, but not mRNA expression, depicted tumor class, underscoring the power of ABPP-MudPIT for the discovery of new markers of human disease that may evade detection by other molecular profiling methods.