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Proteins that contain disulphide bonds are often slow to fold in vitro because the oxidation and correct pairing of the cysteine residues is rate limiting. The folding of such proteins is greatly accelerated in Escherichia coli by DsbA, but the mechanism of this rate enhancement is not well understood. Here we report the crystal structure of oxidized DsbA(More)
Munc18-1 and Syntaxin1 are essential proteins for SNARE-mediated neurotransmission. Munc18-1 participates in synaptic vesicle fusion via dual roles: as a docking/chaperone protein by binding closed Syntaxin1, and as a fusion protein that binds SNARE complexes in a Syntaxin1 N-peptide dependent manner. The two roles are associated with a closed-open(More)
The S-adenosylmethionine-dependent methyltransferase enzymes share little sequence identity, but incorporate a highly conserved structural fold. Surprisingly, residues that bind the common cofactor are poorly conserved, although the binding site is localised to the same region of the fold. The substrate-binding region of the fold varies enormously. Over the(More)
Sec1/Munc18 proteins (SM proteins) bind to soluble NSF attachment protein receptors (SNAREs) and play an essential role in membrane fusion. Divergent modes of regulation have been proposed for different SM proteins indicating that they can either promote or inhibit SNARE assembly. This is in part because of discrete modes of binding that have been described(More)
The debate concerning how many participants represents a sufficient number for interaction testing is well-established and long-running, with prominent contributions arguing that five users provide a good benchmark when seeking to discover interaction problems. We argue that adoption of five users in this context is often done with little understanding of(More)
STUDY OBJECTIVES To examine the validity of self-reported survey estimates of sleep patterns in adolescents through a comparison of retrospective survey descriptions of usual school- and weekend-night sleep habits with diary-reported sleep patterns and actigraphically estimated sleep behaviors over a subsequent week. DESIGN AND SETTING High school(More)
Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, metabolizes and/or bioactivates many endogenous compounds and is implicated in a range of cancers because of its ability to modify diverse promutagen(More)
Human SULT1A1 is primarily responsible for sulfonation of xenobiotics, including the activation of promutagens, and it has been implicated in several forms of cancer. Human SULT1A3 has been shown to be the major sulfotransferase that sulfonates dopamine. These two enzymes shares 93% amino acid sequence identity and have distinct but overlapping substrate(More)
Behavioral scientists have increasingly included inflammatory biology as mechanisms in their investigation of psychosocial dynamics on the pathobiology of disease. However, a lack of standardization of inclusion and exclusion criteria and assessment of relevant control variables impacts the interpretation of these studies. The present paper reviews and(More)
OBJECTIVES To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light. DESIGN Randomized controlled trial. SETTING Two San Diego-area nursing homes. PARTICIPANTS Seventy-seven (58 women, 19 men) nursing home residents participated. Mean age +/- standard deviation was 85.7 +/- 7.3 (range 60-100)(More)